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Title:
FLUORENYLMETHYLOXYCARBONYL AND FLUORENYLMETHYLAMINOCARBONYL COMPOUNDS, PROTEIN CONJUGATES THEREOF, AND METHODS FOR THEIR USE
Document Type and Number:
WIPO Patent Application WO/2022/103983
Kind Code:
A9
Abstract:
Provided herein are compounds, conjugate products thereof, methods, and pharmaceutical compositions for use in treatment and diagnosis.

Inventors:
BAJJURI KRISHNA (US)
Application Number:
PCT/US2021/059014
Publication Date:
June 09, 2022
Filing Date:
November 11, 2021
Export Citation:
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Assignee:
SUTRO BIOPHARMA INC (US)
International Classes:
A61K8/04; A61K47/60; C08G65/332; C08G65/333
Attorney, Agent or Firm:
NOSON, Kevin et al. (US)
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Claims:
WHAT IS CLAIMED IS: 1. A compound according to Formula (I) or (X) (I) (X) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof; wherein RG is a reactive group; POLY is a water soluble polymer; X is a bond, -O-, or -N(R2)-; each of L1, L2, and L3 is, independently, a linker; each R1 is independently hydrogen, an electron donating group, or an electron withdrawing group; wherein either L1 comprises a carbonyl carbon covalently bound to the fluorene, or R1 comprises an electron withdrawing group, or both; R4 is hydrogen or an electron withdrawing group; R2 is hydrogen or lower alkyl; n is an integer selected from one to four; n1 is an integer selected from one to four; m is an integer selected from zero to four; and m2 is an integer selected from one to four. 2. The compound of claim 1, wherein RG is a reactive group; POLY is a water soluble polymer; X is a bond, -O-, or -N(R2)-; each of L1, L2, and L3 is, independently, a linker wherein L1 comprises a carbonyl carbon covalently bound to the fluorene; each R1 is independently hydrogen, an electron donating group, or an electron withdrawing group; R4 is hydrogen or an electron withdrawing group; R2 is hydrogen or lower alkyl; n is an integer selected from one to four; and m is an integer selected from zero to four. 3. The compound of claim 1 or 2, wherein each L1, L2, and L3 is selected from the group consisting of a bond, carbonyl, alkylene, substituted alkylene, heteroalkylene, and substituted heteroalkylene; and wherein either L1 comprises a carbonyl carbon covalently bound to the fluorene, or R1 comprises an electron withdrawing group, or both. 4. The compound of any of the preceding claims, wherein L1 is -X1-C1-C6alkylene-X2-C(O)- wherein X1 and X2 are independently selected from the group consisting of -O-, -S- or -N(R2)-; R2 is hydrogen or lower alkyl; and -C1-C6alkylene- is optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. 5. The compound of any of the preceding claims, wherein L1 is selected from the group consisting of -O-C1-C6alkylene-S-C(O)-, -O-C1-C6alkylene-NH-C(O)-, -S-C1-C6alkylene-O- C(O)-, -S-C1-C6alkylene-NH-C(O)-, -NH-C1-C6alkylene-O-C(O)-, -NH-C1-C6alkylene-S- C(O)-, -O-C1-C6alkylene-N(Me)-C(O)-, -S-C1-C6alkylene-N(Me)-C(O)-, -N(Me)-C1-C6alkylene-O-C(O)-, -N(Me)-C1-C6alkylene-S-C(O)-, -O-C1-C6alkylene-N(Et)-C(O)-, -S-C1-C6alkylene-N(Et)-C(O)-, -N(Et)-C1-C6alkylene-O-C(O)-, and -N(Et)-C1-C6alkylene-S-C(O)-; and each -C1-C6alkylene- is independently optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. 6. The compound of any of the preceding claims, wherein L1 is -O-CH2-CH2-N(H)-C(O)- wherein the carbonyl carbon is covalently bound to the fluorene. 7 The compound of any of the preceding claims, wherein L2 is lower alkylene, -CH2-, -CH2CH2OCH2CH2OCH2CH2-, or -CH2-CH2-C(O)-. 8. The compound of any of the preceding claims, wherein L2 is lower alkylene selected from the group consisting of -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2- , -CH2CH2CH2CH2CH2-, and -CH2CH2CH2CH2CH2CH2- wherein each are independently optionally substituted with one or more substituents independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. 9. The compound of any of the preceding claims, wherein L2 is -CH2- or -CH2CH2-, wherein each are independently optionally substituted with one or more substituents selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. 10. The compound of any of the preceding claims, wherein L3 is lower alkylene. 11. The compound of any of the preceding claims, wherein RG comprises an azide, alkyne, hydrazide, aldehyde, alkoxyamine, -NH2, carboxyl, ester, or maleimide. 12. The compound of claim 11, wherein RG comprises an azide. 13. The compound of claim 11, wherein RG comprises an alkyne. 14. The compound of claim 11, wherein RG comprises a strained alkyne. 15. The compound of claim 11, wherein RG comprises an alkoxyamine. 16. The compound of claim 15, wherein RG is -O-NH2. 17. The compound of claim 14, wherein RG is selected from the group consisting of . 18. The compound of any of the previous claims, wherein the compound is according to Formula (I).

19. The compound of any of the previous claims, wherein the compound is according to Formula (I) and n1 is two. 20. The compound of any of the previous claims, wherein the compound is according to Formula (I) and n1 is one. 21. The compound of any one of claims 1-17, wherein the compound is according to Formula (X) and m2 is two. 22. The compound of any one of claims 1-17, wherein the compound is according to Formula (X) and m2 is one. 23. The compound of any one of claims 1-20, according to Formula (II) wherein RG is a reactive group comprising an alkyne or an azide; POLY is a water soluble polymer; X is -O- or -N(R2)-; L2 is a linker; and R1 is hydrogen, an electron donating group, or an electron withdrawing group. 24. The compound of claim 23, according to Formula (III) or (IV)

wherein POLY is a water soluble polymer; each p is an integer selected from one to eight; and each R1 is hydrogen, an electron donating group, or an electron withdrawing group. 25. The compound of any one of claims 1-17, wherein the compound is according to Formula (X). 26. The compound of any one of claims 1-17, according to Formula (XII) wherein RG is a reactive group comprising an alkyne or an azide; POLY is a water soluble polymer; X is a bond, -O- or -N(R2)-; each L2 and L3 is, independently, a linker; and R4 is hydrogen or an electron withdrawing group. 27. The compound of claim 26, according to Formula (XIII) or (XIV)

wherein POLY is a water soluble polymer; p is an integer selected from zero to eight; each R4 is hydrogen or an electron withdrawing group. 28. The compound of any of the preceding claims, wherein POLY is selected from the group consisting of polyethylene glycol (PEG), polyvinylpyrrolidone, polyglycerol, poly(N- 2-hydroxypropyl) methacrylamide, and polyoxazoline. 29. The compound of any of the preceding claims, wherein POLY is polyethylene glycol (PEG). 30. The compound of any of the preceding claims, wherein POLY has a molecular weight from 5 kDa to 50 kDa. 31. The compound of any of the preceding claims, wherein POLY has a molecular weight from 10 kDa to 25 kDa. 32. The compound of claim 1, selected from the group consisting of

, ,

. 33. The compound of any of the previous claims, wherein each R1 is independently selected from the group consisting of hydrogen, haloalkyl, halogen, -CN, -SO3H, -C(O)R3, - C(O)OR3, -OR3, -N(H)C(O)R3, -N(H)CO2R3, and -N(H)C(O)C(H)(R3)CO2H, and wherein each R3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. 34. The compound of any of the previous claims, wherein each R1 is independently selected from the group consisting of hydrogen, -CF3, -Br, -Cl, -F, -CN, -SO3H, -C(O)Me, - CO2Me, -OMe, -N(H)C(O)Me, -N(H)CO2Me, and -N(H)C(O)C(H)(Me)CO2H. 35. The compound of any of the previous claims, wherein each R4 is independently selected from the group consisting of -C(O)R3, -C(O)OR3, and -S(O)2R3 wherein each R3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. 36. The compound of any of the previous claims wherein each R4 is independently selected from the group consisting of hydrogen, -CF3, -C(O)Me, -CO2Me, and -S(O)2CH3. 37. A conjugate according to Formula (I′) or (X′)

or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof, regioisomer, and/or mixture of regioisomers thereof; wherein each RG′ is independently a divalent residue of a reactive group; each POLY is independently a water soluble polymer; each X is independently a bond, -O-, or -N(R2)-; each L1, L2, and L3 is, independently, a linker; each R1 is independently hydrogen, an electron donating group, or an electron withdrawing group; wherein either L1 comprises a carbonyl carbon covalently bound to the fluorene, or R1 comprises an electron withdrawing group, or both each R4 is hydrogen or an electron withdrawing group; each R2 is independently hydrogen or lower alkyl; each n is independently an integer selected from one to four; each n1 is independently an integer selected from one to four; each m is independently an integer selected from zero to four; each m1 is independently an integer selected from one to four; w is an integer selected from one to ten; and PRO is a macromolecular moiety. 38. The conjugate of claim 37, wherein each RG′ is independently a divalent residue of a reactive group; each POLY is independently a water soluble polymer; each X is independently a bond, -O-, or -N(R2)-; each L1, L2, and L3 is, independently, a linker wherein L1 comprises a carbonyl carbon covalently bound to the fluorene; each R1 is independently hydrogen, an electron donating group, or an electron withdrawing group; each R4 is hydrogen or an electron withdrawing group; each R2 is independently hydrogen or lower alkyl; each n is independently an integer selected from one to four; each m is independently an integer selected from zero to four; w is an integer selected from one to ten; and PRO is a macromolecular moiety. 39. The conjugate of claim 38, wherein each L1, L2, and L3 is independently selected from the group consisting of a bond, carbonyl, alkylene, substituted alkylene, heteroalkylene, and substituted heteroalkylene. 40. The conjugate of any one of claims 37-39, wherein L1 is -X1-C1-C6alkylene-X2-C(O)- wherein X1 and X2 are independently selected from the group consisting of -O-, -S- or -N(R2)-; R2 is hydrogen or lower alkyl; and -C1-C6alkylene- is optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. 41. The conjguate of any one of claims 37-40, wherein L1 is selected from the group consisting of -O-C1-C6alkylene-S-C(O)-, -O-C1-C6alkylene-NH-C(O)-, -S-C1-C6alkylene-O-C(O)-, -S-C1-C6alkylene-NH-C(O)-, -NH-C1-C6alkylene-O-C(O)-, -NH-C1-C6alkylene-S-C(O)-, -O-C1-C6alkylene-N(Me)-C(O)-, -S-C1-C6alkylene-N(Me)- C(O)-, -N(Me)-C1-C6alkylene-O-C(O)-, -N(Me)-C1-C6alkylene-S-C(O)-, -O-C1-C6alkylene-N(Et)-C(O)-, -S-C1-C6alkylene-N(Et)-C(O)-, -N(Et)-C1-C6alkylene-O-C(O)-, and -N(Et)-C1-C6alkylene-S-C(O)-; and each -C1-C6alkylene- is independently optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy.

42. The conjugate of any one of claims 37-41, wherein each L1 is -O-CH2-CH2-N(H)-C(O)- wherein the carbonyl carbon is covalently bound to the fluorene. 43. The conjugate of any one of claims 29-37, wherein each L2 is independently lower alkylene, -CH2-, -CH2CH2OCH2CH2OCH2CH2-, or -CH2-CH2-C(O)-. 44. The conjugate of any one of claims 29-33, wherein L2 is a lower alkylene selected from the group consisting of -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, and -CH2CH2CH2CH2CH2CH2- wherein each are independently optionally substituted with one or more substituents independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. 45. The conjugate of any one of claims 37-44, wherein L2 is -CH2- or -CH2CH2- wherein each are independently, optionally substituted with a group selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. 46. The conjugate of any one of claims 37-45, wherein each L3 is lower alkylene. 47. The conjugate of any one of claims 37-46, wherein each RG′ comprises, independently of each other, a residue of an azide, alkyne, hydrazide, aldehyde, alkoxyamine, amine, carboxyl, ester, or maleimide. 48. The conjugate any one of claims 37-47, wherein each RG′ comprises, independently of each other, a residue of an azide. 49. The conjugate of any one of claims 37-47, wherein each RG′ comprises, independently of each other, a residue of alkyne. 50. The conjugate of any one of claims 37-47, wherein each RG′ comprises, independently of each other, a residue of a strained alkyne. 51. The conjugate of any one of claims 37-47, wherein RG′ comprises, independently of each other, a residue of an alkoxyamine. 52. The conjugate of claim 51, wherein RG′ is -O-NH-.

53. The conjugate of claim 50, wherein each RG′ is independently a divalent residue of a reactive group selected from the group consisting of , , , . 54. The conjugate of any one of claims 37-53, wherein the conjugate is according to Formula (I′). 55. The conjugate of any one of claims 37-54, wherein the conjugate is according to Formula (I′) and n1 is two. 56. The conjugate of any one of claims 37-55, wherein the conjugate is according to Formula (I′) and n1 is one. 57. The conjugate of any one of claims 37-53, wherein the compound is according to Formula (X′) and m1 is two. The conjugate of any one of claims 37-53, wherein the compound is according to Formula (X′) and m1 is one. 59. The conjugate of any one of claims 37-56, according to Formula (II′) wherein each RG′ is independently a divalent group comprising a residue of an alkyne or an azide; each POLY is independently a water soluble polymer; each X is independently -O- or -N(R2)-; each L2 is independently a linker; each R1 is independently hydrogen, an electron donating group, or an electron withdrawing group; w is an integer selected from one to ten; and PRO is a macromolecular moiety. 60. The conjugate of claim 59, according to Formula (III′) or (IV′) wherein each POLY is independently a water soluble polymer; each R1 is independently hydrogen, an electron donating group, or an electron withdrawing group; w is an integer selected from one to ten; and PRO is a macromolecular moiety bound to a triazole nitrogen other than the middle nitrogen of the triazole. 61. The conjugate of any one of claims 37-53, wherein the conjugate is according to Formula (X′). 62. The conjugate of claim 61, according to Formula (XII′) wherein each RG′ is a divalent group comprising a residue of an alkyne or an azide; each POLY is independently a water soluble polymer; each X is independently a bond, -O-, or -N(R2)-; each L2 and L3 is independently a linker; each R4 is independently hydrogen or an electron withdrawing group; w is an integer selected from one to ten; and PRO is a macromolecular moiety. 63. The conjugate of claim 62, according to Formula (XIII′) or (XIV′)

wherein each POLY is independently a water soluble polymer; each p is independently an integer selected from zero to eight; w is an integer selected from one to ten; and each R4 is an electron withdrawing group. 64. The conjugate of any one of claims 37-63, wherein each POLY is independently selected from the group consisting of polyethylene glycol (PEG), polyvinylpyrrolidone, polyglycerol, poly(N-2-hydroxypropyl) methacrylamide, and polyoxazoline. 65. The conjugate of any one of claims 37-64, wherein each POLY is independently polyethylene glycol. 66. The conjugate of any one of claims 37-65, wherein each POLY independently has a molecular weight from 5 kDa to 50 kDa. 67. The conjugate of any one of claims 37-66, wherein each POLY independently has a molecular weight from 10 kDa to 25 kDa. 68. The conjugate of claim 37, selected from the group consisting of

, , ,

,

, ,

. 69. The conjugate of any one of claims 37-68, wherein each R1 is independently selected from the group consisting of hydrogen, haloalkyl, halogen, -CN, -SO3H, -C(O)R3, -C(O)OR3, -OR3, -N(H)C(O)R3, -N(H)CO2R3, and -N(H)C(O)C(H)(R3)CO2H wherein each R3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. 70. The conjugate of any one of claims 37-69, wherein each R1 is independently selected from the group consisting of hydrogen, -CF3, -Br, -Cl, -F, -CN, -SO3H, -C(O)Me, -CO2Me, - OMe, -N(H)C(O)Me, -N(H)CO2Me, and -N(H)C(O)C(H)(Me)CO2H. 71. The conjugate of any one of claims 37-70, wherein each R4 is independently selected from the group consisting of hydrogen, haloalkyl, -C(O)R3, -C(O)OR3, and -S(O)2CH3 wherein each R3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. 72. The conjugate of any one of claims 37-71, wherein each R4 is independently selected from the group consisting of hydrogen, -CF3, -C(O)Me, -CO2Me, and -S(O)2CH3. 73. The conjugate of any one of claims 37-70, wherein PRO is an antibody or an antigen- binding fragment thereof, a protein, or a peptide. 74. The conjugate of any one of claims 37-73, wherein PRO is selected from the group consisting of bone morphogenic protein, erythropoietin, G-CSF, GM-CSF, interferon alpha, interferon beta, interferon gamma, IL-2, and IL-11. 75. The conjugate of any one of claims 37-74, wherein PRO comprises one or more non- natural amino acids suitable for conjugation.

76. The conjugate of claim 75, wherein at least one of the non-natural amino acid residues is a pAMF residue. 77. The conjugate of claim 75, wherein at least one of the non-natural amino acid residues is a para-acetylphenylalanine residue. 78. The conjugate of claim 75, wherein PRO is an antibody or an antigen binding fragment thereof, comprising a Y180 pAMF mutation, a F404 pAMF mutation, or both. 79. A pharmaceutical composition comprising the conjugate of any one of claims 37-78, and a pharmaceutically acceptable carrier. 80. A method for treating or preventing a disease or condition in a subject in need thereof comprising administering to the subject an effective amount of the conjugate of any one of claims 37-78, or the pharmaceutical composition of claim 79. 81. A method of diagnosing a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of the conjugate of any one of claims 37-78, or the pharmaceutical composition of claim 79. 82. The method of claim 80 or 81, wherein the disease or condition is a cancer. 83. The method of claim 80 or 81, wherein the disease or condition is an inflammatory disease. 84. The method of claim 80 or 81, wherein said conjugate or pharmaceutical composition is administered in combination or alternation with a second agent. 85. A process for preparing the conjugate of any one of claims 37-78, the process comprising (i) contacting PRO with a compound of any of claims 1-36 under conditions sufficient for forming a bond between PRO and the compound; wherein PRO comprises a moiety capable of reacting with the compound.

Description:
FLUORENYLMETHYLOXYCARBONYL AND FLUORENYLMETHYLAMINOCARBONYL COMPOUNDS, PROTEIN CONJUGATES THEREOF, AND METHODS FOR THEIR USE CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit under 35 U.S.C. § 119 of U.S. provisional application no.63/112,536, filed November 11, 2020, the content of which is hereby incorporated by reference in its entirety. FIELD [0002] Provided herein are fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl compounds, and macromolecule conjugates thereof; pharmaceutical compositions comprising the compounds and/or conjugates; methods of producing the compounds and/or conjugates; and methods of using the compounds, conjugates, and compositions for therapy. The compounds, conjugates, and compositions are useful, for instance, in methods of treatment and prevention of cell proliferation and cancer, methods of detection of cell proliferation and cancer, and methods of diagnosis of cell proliferation and cancer. The compounds, conjugates, and compositions are also useful in methods of treatment, prevention, detection, and diagnosis of inflammatory diseases or conditions. BACKGROUND [0003] Biotherapeutics provide a wealth of treatment and diagnostic potential for patients worldwide. However, many drugs based on macromolecules, such as proteins, peptides, and antibodies, present limitations on their effective use, including limitations on bioavailability, absorption, distribution, metabolism, and excretion (ADME). Some of these limitations can affect drug dosage, half-life, side effects, and toxicities. For instance, systemic administration of IL-2 has been associated with rapid clearance, toxicity, and a narrow therapeutic index. Shaker et al., 2009, J. Pharm. Sci 98(7):2268-2298. Strategies for improving the effectiveness of biotherapeutics remain needed. SUMMARY [0004] Provided herein are fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl compounds of Formulas (I), (X), and sub-formulas thereof, compositions comprising the compounds, methods of producing the compounds, and methods of using the compounds, conjugates, and compositions in treatment and diagnosis. The compounds of Formula (I), (X), and sub-formulas and embodiments thereof, are useful for modulating the bioavailability and ADME of macromolecular compounds. In certain embodiments, the compounds can be used to prepare prodrug conjugates of macromolecular compounds for use in vivo or elsewhere. In certain embodiments, the compounds and conjugates feature electron withdrawing groups on fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl cores. These electron withdrawing groups can be varied to tune the plasma stability of the conjugates. This provides a platform for modulating the bioavailability and ADME of a macromolecule in vivo. [0005] In one aspect, provided is a compound of Formula (I) or (X) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof; wherein RG is a reactive group; POLY is a water soluble polymer; X is a bond, -O-, or -N(R 2 )-; each of L 1 , L 2 , and L 3 is, independently, a linker; each R 1 is independently hydrogen, an electron donating group, or an electron withdrawing group; wherein either L 1 comprises a carbonyl carbon covalently bound to the fluorene, or R 1 comprises an electron withdrawing group, or both; R 4 is hydrogen or an electron withdrawing group; R 2 is hydrogen or lower alkyl; n is an integer selected from one to four; n1 is an integer selected from one to four; m is an integer selected from zero to four; and m2 is an integer selected from one to four. [0006] In one aspect, provided is a compound of Formula (I) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof; wherein RG is a reactive group; POLY is a water soluble polymer; X is a bond, -O-, or -N(R 2 )-; each of L 1 and L 2 is, independently, a linker wherein L 1 comprises a carbonyl carbon covalently bound to the fluorene; each R 1 is independently hydrogen, an electron donating group, or an electron withdrawing group; R 2 is hydrogen or lower alkyl; and n is an integer selected from one to four. [0007] In certain embodiments, provided is a compound of Formula (X): or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof; wherein RG is a reactive group; POLY is a water soluble polymer; X is a bond, -O-, or -N(R 2 )-; each of L 1 , L 2 , and L 3 is, independently, a linker wherein L 1 comprises a carbonyl carbon covalently bound to the fluorene; each R 1 is independently hydrogen, an electron donating group, or an electron withdrawing group; R 4 is hydrogen or an electron withdrawing group; R 2 is hydrogen or lower alkyl; and m is an integer selected from zero to four. [0008] In a second aspect, provided are conjugates comprising residues of compounds of Formula (I) or (X), and sub formulas and embodiments thereof. In certain embodiments, the conjugates are according to or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof, regioisomer, and/or mixture of regioisomers thereof; wherein each RG′ is independently a divalent residue of a reactive group; each POLY is independently a water soluble polymer; each X is independently a bond, -O-, or -N(R 2 )-; each L 1 , L 2 , and L 3 is, independently, a linker; each R 1 is independently hydrogen, an electron donating group, or an electron withdrawing group; wherein either L 1 comprises a carbonyl carbon covalently bound to the fluorene, or R 1 comprises an electron withdrawing group, or both R 4 is hydrogen or an electron withdrawing group; each R 2 is independently hydrogen or lower alkyl; each n is independently an integer selected from one to four; each n1 is independently an integer selected from one to four; each m is independently an integer selected from zero to four each m1 is independently an integer selected from one to four; w is an integer selected from one to ten; and PRO is a macromolecular moiety. [0009] In another aspect, provided are conjugates comprising residues of compounds of Formula (I) or (X), and sub formulas and embodiments thereof. In certain embodiments, the conjugate is according to Formula (I′), wherein each RG′ is independently a divalent residue of a reactive group; each POLY is independently a water soluble polymer; each X is independently a bond, -O-, or -N(R 2 )-; each of L 1 and L 2 is, independently, a linker wherein L 1 comprises a carbonyl carbon covalently bound to the fluorene; each R 1 is independently hydrogen, an electron donating group, or an electron withdrawing group; each R 2 is independently hydrogen or lower alkyl; each n is independently an integer selected from one to four; PRO is a macromolecular moiety; and w is an integer selected from one to ten; or a pharmaceutically acceptable salt, solvate, stereoisomer, tautomer, and/or mixture of regioisomers thereof. [0010] In certain embodiments, the conjugate is according to Formula (X′), wherein each RG′ is independently a divalent residue of a reactive group; each POLY is independently a water soluble polymer; each X is independently a bond, -O-, or -N(R 2 )-; each of L 1 , L 2 , and L 3 is, independently, a linker wherein L 1 comprises a carbonyl carbon covalently bound to the fluorene; each R 1 is independently hydrogen, an electron donating group, or an electron withdrawing group; each R 4 is hydrogen or an electron withdrawing group; each R 2 is independently hydrogen or lower alkyl; each m is independently an integer selected from zero to four; PRO is a macromolecular moiety; and w is an integer selected from one to ten; or a pharmaceutically acceptable salt, solvate, stereoisomer, tautomer, and/or mixture of regioisomers thereof. [0011] In certain aspects, the conjugates are useful in methods of treatment and prevention of cell proliferation and cancer, methods of detection of cell proliferation and cancer, and methods of diagnosis of cell proliferation and cancer. In certain aspects, the conjugates are also useful in methods of treatment and prevention of inflammatory diseases and conditions. [0012] In another aspect, provided are compositions comprising a compound of Formula (I) or (X), or certain embodiments thereof, or a conjugate of Formula (I′) or (X′), or certain embodiments thereof. In some embodiments, the compositions are pharmaceutical compositions. Any suitable pharmaceutical composition may be used. In a further aspect, provided herein is a kit comprising the compound of Formula (I) or (X), or embodiments thereof, or a conjugate of Formula (I′) or (X′), or a pharmaceutical composition thereof. [0013] In another aspect, provided herein are methods of using the compounds or the conjugates described herein. In some embodiments, the methods are for delivering one or more macromolecules to a target cell or tissue. In some embodiments, the methods are for treatment. In some embodiments, the methods are diagnostic methods. In some embodiments, the methods are analytical methods. In some embodiments, the compounds or conjugates described herein are used to treat a disease or condition. In some aspects, the disease or condition is selected from a cancer, and/or an inflammatory disease or condition. [0014] Also provided herein is the use of compounds described herein, and conjugates thereof, for the treatment of cancer, and/or an inflammatory disease or condition. BRIEF DESCRIPTION OF THE FIGURES [0015] FIGS. 1 and 2 show protein conjugation and subsequent release of functionalized fluorenylmethyloxycarbonyl compounds [0016] FIG. 3 is an SDS-PAGE gel showing release of the PEG from the compound A conjugate. [0017] FIG.4 is an SDS-PAGE gel showing conjugation efficiency. DESCRIPTION OF EXEMPLARY EMBODIMENTS [0018] Described herein are fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl compounds, and conjugates thereof, useful for modulating the bioavailability and ADME of macromolecular compounds. In some instances, the compounds described herein are useful for preparing conjugates, for instance prodrugs, of macromolecules for in vivo use. Definitions [0019] Unless otherwise defined, all terms of art, notations and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this disclosure pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and/or ready reference. The techniques and procedures described or referenced herein are generally well understood and are commonly employed using conventional methodologies by those skilled in the art, for example, the widely utilized molecular cloning methodologies described in Green & Sambrook, Molecular Cloning: A Laboratory Manual 4 th ed. (2012), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; and Ausubel et al., Current Protocols in Molecular Biology, John Wiley & Sons. As appropriate, procedures involving the use of commercially available kits and reagents are generally carried out in accordance with manufacturer-defined protocols and conditions unless otherwise noted. [0020] As used herein, the singular forms “a,” “an,” and “the” include the plural referents unless the context clearly indicates otherwise. [0021] The term “about” indicates and encompasses an indicated value and a range above and below that value. In certain embodiments, the term “about” indicates the designated value ± 10%, ± 5%, or ± 1%. In certain embodiments, the term “about” indicates the designated value ± one standard deviation of that value. In certain embodiments, for example, logarithmic scales (e.g., pH), the term “about” indicates the designated value ± 0.3, ±0.2, or ± 0.1. [0022] When referring to the compounds provided herein, the following terms have the following meanings unless indicated otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art. In the event that there is a plurality of definitions for a term herein, those in this section prevail unless stated otherwise. [0023] “Alkoxy” and “alkoxyl,” refer to the group –OR′′ where R′′ is alkyl or cycloalkyl. Alkoxy groups include, in certain embodiments, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, and the like. [0024] The term “alkoxyamine,” as used herein, refers to the group -alkylene-O-NH 2 , wherein alkylene is as defined herein. In some embodiments, alkoxyamine groups can react with aldehydes to form oxime residues. Examples of alkoxyamine groups include -CH 2 CH 2 -O-NH 2 and -CH 2 -O-NH 2 . [0025] The term “alkyl,” as used herein, unless otherwise specified, refers to a saturated straight or branched hydrocarbon. In certain embodiments, the alkyl group is a primary, secondary, or tertiary hydrocarbon. In certain embodiments, the alkyl group includes one to ten carbon atoms (i.e., C 1 to C 10 alkyl). In certain embodiments, the alkyl is a lower alkyl , for example, C1-6alkyl, and the like. In certain embodiments, the alkyl group is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secbutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, isohexyl, 3-methylpentyl, 2,2-dimethylbutyl, and 2,3- dimethylbutyl. In certain embodiments, “substituted alkyl” refers to an alkyl substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In some embodiments, alkyl is unsubstituted. [0026] The term “alkylene,” as used herein, unless otherwise specified, refers to a divalent alkyl group, as defined herein. “Substituted alkylene” refers to an alkylene group substituted as described herein for alkyl. In some embodiments, alkylene is unsubstituted. [0027] “Alkenyl” refers to an olefinically unsaturated hydrocarbon group, in certain embodiments, having up to about eleven carbon atoms or from two to six carbon atoms (e.g., “lower alkenyl”), which can be straight-chained or branched, and having at least one or from one to two sites of olefinic unsaturation. “Substituted alkenyl” refers to an alkenyl group substituted as described herein for alkyl. [0028] “Alkenylene” refers to a divalent alkenyl as defined herein. Lower alkenylene is, for example, C 2 -C 6 -alkenylene. [0029] “Alkynyl” refers to acetylenically unsaturated hydrocarbon groups, in certain embodiments, having up to about eleven carbon atoms or from two to six carbon atoms (e.g., “lower alkynyl”), which can be straight-chained or branched, and having at least one or from one to two sites of acetylenic unsaturation. Non-limiting examples of alkynyl groups include acetylene (-C≡CH), propargyl (-CH2C≡CH), and the like. “Substituted alkynyl” refers to an alkynyl group substituted as described herein for alkyl. [0030] “Alkynylene” refers to a divalent alkynyl as defined herein. Lower alkynylene is, for example, C 2 -C 6 -alkynylene. [0031] “Amino” refers to -NH2. [0032] The term “alkylamino,” as used herein, and unless otherwise specified, refers to the group –NHR′′ where R′′ is, for example, C1-10alkyl, as defined herein. In certain embodiments, alkylamino is C 1-6 alkylamino. [0033] The term “dialkylamino,” as used herein, and unless otherwise specified, refers to the group –NR′′R′′ where each R′′ is independently C1-10alkyl, as defined herein. In certain embodiments, dialkylamino is di-C 1-6 alkylamino. [0034] The term “aryl,” as used herein, and unless otherwise specified, refers to phenyl, biphenyl, or naphthyl. The term includes both substituted and unsubstituted moieties. An aryl group can be substituted with any described moiety including, but not limited to, one or more moieties (e.g., in some embodiments one, two, or three moieties) selected from the group consisting of halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate, wherein each moiety is independently either unprotected, or protected as necessary, as would be appreciated by those skilled in the art (e.g., Greene, et al., Protective Groups in Organic Synthesis, John Wiley and Sons, Second Edition, 1991); and wherein the aryl in the arylamino and aryloxy substituents are not further substituted. [0035] The term “arylamino,” as used herein, and unless otherwise specified, refers to an - NR′R′′ group where R′ is hydrogen or C1-C6-alkyl; and R′′ is aryl, as defined herein. [0036] The term “arylene,” as used herein, and unless otherwise specified, refers to a divalent aryl group, as defined herein. [0037] The term “aryloxy,” as used herein, and unless otherwise specified, refers to an -OR group where R is aryl, as defined herein. [0038] “Alkarylene” refers to an arylene group, as defined herein, wherein the aryl ring is substituted with one or two alkyl groups. “Substituted alkarylene” refers to an alkarylene, as defined herein, where the arylene group is further substituted, as defined herein for aryl. [0039] “Aralkylene” refers to an -CH 2 -arylene-, -arylene-CH 2 -, or -CH 2 -arylene-CH 2 - group, where arylene is as defined herein. “Substituted aralkylene” refers to an aralkylene, as defined herein, where the aralkylene group is substituted, as defined herein for aryl. [0040] “Carboxyl” or “carboxy” refers to -C(O)OH or -COOH. [0041] The term “cycloalkyl,” as used herein, unless otherwise specified, refers to a saturated cyclic hydrocarbon. In certain embodiments, the cycloalkyl group may be a saturated, and/or bridged, and/or non-bridged, and/or a fused bicyclic group. In certain embodiments, the cycloalkyl group includes three to ten carbon atoms (i.e., C3 to C10 cycloalkyl). In some embodiments, the cycloalkyl has from three to fifteen carbons (C 3-15 ), from three to ten carbons (C3-10), from three to seven carbons (C3-7), or from three to six carbons (C3-C6) (i.e., “lower cycloalkyl”). In certain embodiments, the cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexylmethyl, cycloheptyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, decalinyl, or adamantyl. [0042] The term “cycloalkylene,” as used herein refers to a divalent cycloalkyl group, as defined herein. In certain embodiments, the cycloalkylene group is cyclopropylene , cyclobutylene , cyclopentylene , cyclohexylene , cycloheptylene , and the like. Lower cycloalkylene refers to a C 3 -C 6 -cycloalkylene. [0043] The term “cycloalkylalkyl,” as used herein, unless otherwise specified, refers to an alkyl group, as defined herein, substituted with one or two cycloalkyl, as defined herein. [0044] The term “ester,” as used herein, refers to -C(O)OR or -COOR where R is alkyl, as defined herein. [0045] The term “fluorene” as used herein refers to , wherein any one or more carbons bearing one or more hydrogens can be substituted with a chemical functional group as described herein. [0046] The term “haloalkyl” refers to an alkyl group, as defined herein, substituted with one or more halogen atoms (e.g., in some embodiments one, two, three, four, or five) which are independently selected. [0047] The term “heteroalkyl” refers to an alkyl, as defined herein, in which one or more carbon atoms are replaced by heteroatoms. As used herein, “heteroalkenyl” refers to an alkenyl, as defined herein, in which one or more carbon atoms are replaced by heteroatoms. As used herein, “heteroalkynyl” refers to an alkynyl, as defined herein, in which one or more carbon atoms are replaced by heteroatoms. Suitable heteroatoms include, but are not limited to, nitrogen (N), oxygen (O), and sulfur (S) atoms. Heteroalkyl, heteroalkenyl, and heteroalkynyl are optionally substituted. Examples of heteroalkyl moieties include, but are not limited to, aminoalkyl, sulfonylalkyl, and sulfinylalkyl. Examples of heteroalkyl moieties also include, but are not limited to, methylamino, methylsulfonyl, and methylsulfinyl. “Substituted heteroalkyl” refers to heteroalkyl substituted with one, two, or three groups independently selected from halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In some embodiments, a heteroalkyl group may comprise one, two, three, or four heteroatoms. Those of skill in the art will recognize that a 4- membered heteroalkyl may generally comprise one or two heteroatoms, a 5- or 6-membered heteroalkyl may generally comprise one, two, or three heteroatoms, and a 7- to 10-membered heteroalkyl may generally comprise one, two, three, or four heteroatoms. [0048] The term “heteroalkylene,” as used herein, refers to a divalent heteroalkyl, as defined herein. “Substituted heteroalkylene” refers to a divalent heteroalkyl, as defined herein, substituted as described for heteroalkyl. [0049] The term “heterocycloalkyl” refers to a monovalent, monocyclic, or multicyclic non- aromatic ring system, wherein one or more of the ring atoms are heteroatoms independently selected from oxygen (O), sulfur (S), and nitrogen (N) (e.g., where the nitrogen or sulfur atoms may be optionally oxidized, and the nitrogen atoms may be optionally quaternized) and the remaining ring atoms of the non-aromatic ring are carbon atoms. In certain embodiments, heterocycloalkyl is a monovalent, monocyclic, or multicyclic fully-saturated ring system. In certain embodiments, the heterocycloalkyl group has from three to twenty, from three to fifteen, from three to ten, from three to eight, from four to seven, from four to eleven, or from five to six ring atoms. The heterocycloalkyl may be attached to a core structure at any heteroatom or carbon atom which results in the creation of a stable compound. In certain embodiments, the heterocycloalkyl is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include a fused or bridged ring system and in which the nitrogen or sulfur atoms may be optionally oxidized, and/or the nitrogen atoms may be optionally quaternized. In some embodiments, heterocycloalkyl radicals include, but are not limited to, 2,5- diazabicyclo[2.2.2]octanyl, decahydroisoquinolinyl, dihydrobenzisoxazinyl, dihydrofuryl, dihydroisoindolyl, dihydropyranyl, dihydropyrazolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dioxolanyl, 1,4-dithianyl, furanonyl, imidazolidinyl, imidazolinyl, indolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, oxazolidinonyl, oxazolidinyl, oxiranyl, piperazinyl, piperidinyl, 4- piperidonyl, pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolinyl, quinuclidinyl, tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydrothienyl, thiamorpholinyl, thiazolidinyl, tetrahydroquinolinyl, and 1,3,5-trithianyl. In certain embodiments, heterocycloalkyl may also be optionally substituted as described herein. In certain embodiments, heterocycloalkyl is substituted with one, two, or three groups independently selected from halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In some embodiments, a heterocycloalkyl group may comprise one, two, three, or four heteroatoms. Those of skill in the art will recognize that a 4-membered heterocycloalkyl may generally comprise one or two heteroatoms, a 5 or 6-membered heterocycloalkyl may generally comprise one, two, or three heteroatoms, and a 7- to 10-membered heterocycloalkyl may generally comprise one, two, three, or four heteroatoms. [0050] “Heterocycloalkylene” refers to a divalent heterocycloalkyl as defined herein. [0051] The term “heteroaryl” refers to a monovalent monocyclic aromatic group and/or multicyclic aromatic group, wherein at least one aromatic ring contains one or more heteroatoms independently selected from oxygen, sulfur, and nitrogen in the ring. Each ring of a heteroaryl group can contain one or two oxygen atoms, one or two sulfur atoms, and/or one to four nitrogen atoms, provided that the total number of heteroatoms in each ring is four or less and each ring contains at least one carbon atom. In certain embodiments, the heteroaryl has from five to twenty, from five to fifteen, or from five to ten ring atoms. A heteroaryl may be attached to the rest of the molecule via a nitrogen or a carbon atom. In some embodiments, monocyclic heteroaryl groups include, but are not limited to, furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, triazolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, and triazinyl. Examples of bicyclic heteroaryl groups include, but are not limited to, benzofuranyl, benzimidazolyl, benzoisoxazolyl, benzopyranyl, benzothiadiazolyl, benzothiazolyl, benzothienyl, benzotriazolyl, benzoxazolyl, furopyridyl, imidazopyridinyl, imidazothiazolyl, indolizinyl, indolyl, indazolyl, isobenzofuranyl, isobenzothienyl, isoindolyl, isoquinolinyl, naphthyridinyl, oxazolopyridinyl, phthalazinyl, pteridinyl, purinyl, pyridopyridyl, pyrrolopyridyl, quinolinyl, quinoxalinyl, quinazolinyl, thiadiazolopyrimidyl, and thienopyridyl. Examples of tricyclic heteroaryl groups include, but are not limited to, acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, perimidinyl, phenanthrolinyl, phenanthridinyl, phenarsazinyl, phenazinyl, phenothiazinyl, phenoxazinyl, and xanthenyl. In certain embodiments, heteroaryl may also be optionally substituted as described herein. “Substituted heteroaryl” is a heteroaryl substituted as defined for aryl. [0052] The term “heteroarylene” refers to a divalent heteroaryl group, as defined herein. “Substituted heteroarylene” is a heteroarylene substituted as defined for aryl. [0053] The term “protecting group,” as used herein, and unless otherwise specified, refers to a group that is added to an oxygen, nitrogen, or phosphorus atom to prevent its further reaction, or for other purposes. A wide variety of oxygen and nitrogen protecting groups are known to those skilled in the art of organic synthesis. (See, e.g., Greene, et al., Protective Groups in Organic Synthesis, John Wiley and Sons, Fourth Edition, 2006, which is incorporated herein by reference.) [0054] “Pharmaceutically acceptable salt” refers to any salt of a compound provided herein which retains its biological properties and which is not toxic or otherwise undesirable for pharmaceutical use. Such salts may be derived from a variety of organic and inorganic counter- ions well known in the art. Such salts include, but are not limited to (1) acid addition salts formed with organic or inorganic acids such as hydrochloric, hydrobromic, sulfuric, nitric, phosphoric, sulfamic, acetic, trifluoroacetic, trichloroacetic, propionic, hexanoic, cyclopentylpropionic, glycolic, glutaric, pyruvic, lactic, malonic, succinic, sorbic, ascorbic, malic, maleic, fumaric, tartaric, citric, benzoic, 3-(4-hydroxybenzoyl)benzoic, picric, cinnamic, mandelic, phthalic, lauric, methanesulfonic, ethanesulfonic, 1,2-ethane-disulfonic, 2-hydroxyethanesulfonic, benzenesulfonic, 4-chlorobenzenesulfonic, 2-naphthalenesulfonic, 4-toluenesulfonic, camphoric, camphorsulfonic, 4-methylbicyclo[2.2.2]-oct-2-ene-1- carboxylic, glucoheptonic, 3-phenylpropionic, trimethylacetic, tert-butylacetic, lauryl sulfuric, gluconic, glutamic, hydroxynaphthoic, salicylic, stearic, cyclohexylsulfamic, quinic, muconic acid, and the like; or (2) salts formed when an acidic proton present in the parent compound either (a) is replaced by a metal ion, for example, an alkali metal ion, an alkaline earth ion, or an aluminum ion, or alkali metal or alkaline earth metal hydroxides, such as sodium, potassium, calcium, magnesium, aluminum, lithium, zinc, and barium hydroxide, or ammonia; or (b) coordinates with an organic base, such as aliphatic, alicyclic, or aromatic organic amines, including, without limitation, ammonia, methylamine, dimethylamine, diethylamine, picoline, ethanolamine, diethanolamine, triethanolamine, ethylenediamine, lysine, arginine, ornithine, choline, N,N′-dibenzylethylene-diamine, chloroprocaine, procaine, N-benzylphenethylamine, N-methylglucamine piperazine, tris(hydroxymethyl)-aminomethane, tetramethylammonium hydroxide, and the like. [0055] Pharmaceutically acceptable salts further include, by way of example and without limitation, sodium, potassium, calcium, magnesium, ammonium, and tetraalkylammonium salts, and the like, and when the compound contains a basic functionality, salts of non-toxic organic or inorganic acids, such as hydrohalides, for example, hydrochloride and hydrobromide, sulfate, phosphate, sulfamate, nitrate, acetate, trifluoroacetate, trichloroacetate, propionate, hexanoate, cyclopentylpropionate, glycolate, glutarate, pyruvate, lactate, malonate, succinate, sorbate, ascorbate, malate, maleate, fumarate, tartarate, citrate, benzoate, 3-(4-hydroxybenzoyl)benzoate, picrate, cinnamate, mandelate, phthalate, laurate, methanesulfonate (mesylate), ethanesulfonate, 1,2-ethane-disulfonate, 2-hydroxyethanesulfonate, benzenesulfonate (besylate), 4-chlorobenzenesulfonate, 2-naphthalenesulfonate, 4-toluenesulfonate, camphorate, camphorsulfonate, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylate, glucoheptonate, 3-phenylpropionate, trimethylacetate, tert-butylacetate, lauryl sulfate, gluconate, glutamate, hydroxynaphthoate, salicylate, stearate, cyclohexylsulfamate, quinate, muconate, and the like. [0056] The term “substantially free of” or “substantially in the absence of” with respect to a composition refers to a composition that includes at least 85% or 90% by weight, in certain embodiments 95%, 98 %, 99%, or 100% by weight; or in certain embodiments, 95%, 98%, 99%, or 100% of the designated enantiomer or diastereomer of a compound. In certain embodiments, in the methods and compounds provided herein, the compounds are substantially free of one of two enantiomers. In certain embodiments, in the methods and compounds provided herein, the compounds are substantially free of one of two diastereomers. In certain embodiments, in the methods and compounds provided herein, the compounds are substantially free of enantiomers (i.e., a racemic or 50:50 mixture of compounds). [0057] Similarly, the term “isolated” with respect to a composition refers to a composition that includes at least 85%, 90%, 95%, 98%, or 99% to 100% by weight, of the compound, the remainder comprising other chemical species, enantiomers or diastereomers. [0058] “Solvate” refers to a compound provided herein, or a salt thereof, that further includes a stoichiometric or non-stoichiometric amount of solvent bound by non-covalent intermolecular forces. Where the solvent is water, the solvate is a hydrate. [0059] “Isotopic composition” refers to the amount of each isotope present for a given atom, and “natural isotopic composition” refers to the naturally occurring isotopic composition or abundance for a given atom. Atoms containing their natural isotopic composition may also be referred to herein as “non-enriched” atoms. Unless otherwise designated, the atoms of the compounds recited herein are meant to represent any stable isotope of that atom. For example, unless otherwise stated, when a position is designated specifically as hydrogen (H), the position is understood to have hydrogen at its natural isotopic composition. [0060] “Isotopic enrichment” refers to the percentage of incorporation of an amount of a specific isotope at a given atom in a molecule in the place of that atom’s natural isotopic abundance. For example, deuterium (D) enrichment of 1% at a given position means that 1% of the molecules in a given sample contain deuterium at the specified position. Because the naturally occurring distribution of deuterium is about 0.0156%, deuterium enrichment at any position in a compound synthesized using non-enriched starting materials is about 0.0156%. The isotopic enrichment of the compounds provided herein can be determined using conventional analytical methods known to one of ordinary skill in the art, including mass spectrometry and nuclear magnetic resonance spectroscopy. [0061] “Isotopically enriched” refers to an atom having an isotopic composition other than the natural isotopic composition of that atom. “Isotopically enriched” may also refer to a compound containing at least one atom having an isotopic composition other than the natural isotopic composition of that atom. [0062] As used herein, “alkyl,” “alkylene,” “alkylamino,” “dialkylamino,” “cycloalkyl,” “aryl,” “arylene,” “alkoxy,” “amino,” “carboxyl,” “heterocycloalkyl,” “heteroaryl,” “heteroarylene,” “carboxyl,” and “amino acid” groups optionally comprise deuterium (D) at one or more positions where hydrogen (H) atoms are present, and wherein the deuterium composition of the atom or atoms is other than the natural isotopic composition. [0063] Also as used herein, “alkyl,” “alkylene,” “alkylamino,” “dialkylamino,” “cycloalkyl,” “aryl,” “arylene,” “alkoxy,” “amino,” “carboxyl,” “heterocycloalkyl,” “heteroaryl,” “heteroarylene,” “carboxyl,” and “amino acid” groups optionally comprise carbon-13 ( 13 C) at an amount other than the natural isotopic composition. [0064] The term “macromolecule” or “macromolecular moiety” refers to a protein, peptide, antibody, nucleic acid, carbohydrate, or other large molecule composed of polymerized monomers. They include peptides of two or more residues, or ten or more residues. In certain embodiments, a macromolecule is at least 1000 Da in mass. In certain embodiments, a macromolecule has at least 1000 atoms. In certain embodiments, a macromolecule can be modified. For instance, a protein, peptide, or antibody can be modified with one or more carbohydrates. [0065] The term “immunoglobulin” refers to a class of structurally related proteins generally comprising two pairs of polypeptide chains: one pair of light (L) chains, and one pair of heavy (H) chains. In an “intact immunoglobulin,” all four of these chains are interconnected by disulfide bonds. The structure of immunoglobulins has been well characterized. See, e.g., Paul, Fundamental Immunology 7th ed., Ch.5 (2013) Lippincott Williams & Wilkins, Philadelphia, PA. Briefly, each heavy chain typically comprises a heavy chain variable region (VH or VH) and a heavy chain constant region (C H or CH). The heavy chain constant region typically comprises three domains, abbreviated C H 1 (or CH1), C H 2 (or CH2), and C H 3 (or CH3). Each light chain typically comprises a light chain variable region (VL or VL) and a light chain constant region. The light chain constant region typically comprises one domain, abbreviated CL or CL. [0066] The term “antibody” is used herein in its broadest sense. An antibody includes intact antibodies (e.g., intact immunoglobulins), and antibody fragments (e.g., antigen binding fragments or antigen-binding fragments of antibodies). Antibodies comprise at least one antigen-binding domain. One example of an antigen-binding domain is an antigen binding domain formed by a V H -V L dimer. [0067] The term “amino acid” refers to the twenty common naturally occurring amino acids. Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C); glutamic acid (Glu; E), glutamine (Gln; Q), Glycine (Gly; G); histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V), and the less common pyrrolysine and selenocysteine. Natural amino acids also include citrulline. Naturally encoded amino acids include post-translational variants of the twenty-two naturally occurring amino acids such as prenylated amino acids, isoprenylated amino acids, myrisoylated amino acids, palmitoylated amino acids, N-linked glycosylated amino acids, O-linked glycosylated amino acids, phosphorylated amino acids, and acylated amino acids. The term “amino acid” also includes non-natural (or unnatural) or synthetic ^-, ^-, ^-, or ^- amino acids, and includes, but is not limited to, amino acids found in proteins, i.e. glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline, serine, threonine, cysteine, tyrosine, asparagine, glutamine, aspartate, glutamate, lysine, arginine, and histidine. In certain embodiments, the amino acid is in the L-configuration. In certain embodiments, the amino acid is in the D-configuration. Alternatively, the amino acid can be a derivative of alanyl, valinyl, leucinyl, isoleucinyl, prolinyl, phenylalaninyl, tryptophanyl, methioninyl, glycinyl, serinyl, threoninyl, cysteinyl, tyrosinyl, asparaginyl, glutaminyl, aspartoyl, glutaroyl, lysinyl, argininyl, histidinyl, ^-alanyl, ^-valinyl, ^-leucinyl, ^-isoleuccinyl, ^-prolinyl, ^- phenylalaninyl, ^-tryptophanyl, ^-methioninyl, ^-glycinyl, ^-serinyl, ^-threoninyl, ^- cysteinyl, ^-tyrosinyl, ^-asparaginyl, ^-glutaminyl, ^-aspartoyl, ^-glutaroyl, ^-lysinyl, ^- argininyl, or ^-histidinyl. Unnatural amino acids are not proteinogenic amino acids, or post- translationally modified variants thereof. In particular, the term unnatural amino acid refers to an amino acid that is not one of the twenty common amino acids or pyrrolysine or selenocysteine, or post-translationally modified variants thereof. [0068] The term “conjugate” refers to a fluorenylmethyloxycarbonyl or fluorenylmethylaminocarbonyl compound described herein linked to one or more macromolecular moieties. The macromolecular moiety is as defined herein or is any macromolecule deemed suitable to the person of skill in the art. The compound can be any compound described herein. The fluorenylmethyloxycarbonyl or fluorenylmethylaminocarbonyl compound can be directly linked to the macromolecular moiety via a covalent bond, or the fluorenylmethyloxycarbonyl or fluorenylmethylaminocarbonyl compound can be linked to the macromolecular moiety indirectly via a linker. Typically, the linker is covalently bonded to the macromolecular moiety and also covalently bonded to the fluorenylmethyloxycarbonyl or fluorenylmethylaminocarbonyl compound. [0069] “pAMF,” “pAMF residue,” or “pAMF mutation” refers to a variant phenylalanine residue (i.e., para-azidomethyl-L-phenylalanine) added or substituted into a polypeptide. [0070] The term “linker” refers to a molecular moiety that is capable of forming at least two covalent bonds. Typically, a linker is capable of forming at least one covalent bond to a macromolecular moiety and at least another covalent bond to a fluorenylmethyloxycarbonyl or fluorenylmethylaminocarbonyl compound. In certain embodiments, a linker can form more than one covalent bond to a macromolecular moiety. In certain embodiments, a linker can form more than one covalent bond to a fluorenylmethyloxycarbonyl or fluorenylmethylaminocarbonyl compound or can form covalent bonds to more than one fluorenylmethyloxycarbonyl or fluorenylmethylaminocarbonyl compound. After a linker forms a bond to a macromolecular moiety, or a fluorenylmethyloxycarbonyl or fluorenylmethylaminocarbonyl compound, or both, the remaining structure(i.e. the residue of the linker (“linker residue”) after one or more covalent bonds are formed) may still be referred to as a “linker” herein. The term “linker precursor” refers to a linker having one or more reactive groups capable of forming a covalent bond with a macromolecule, or fluorenylmethoxycarbonyl, or fluorenylaminocarbonyl compound, or both. A person of ordinary skill in the art, given the context of how the term linker is used, would understand whether “linker” means linker precursor with one reactive group, a linker precursor with more than one reactive groups, a linker residue which is covalently bonded to the macromolecule, a linker residue which is covalently bonded to a fluorenylmethyloxycarbonyl or fluorenylmethylaminocarbonyl compound, and/or a linker residue which is covalently bonded to the macromolecule and is covalently bonded to a fluorenylmethyloxycarbonyl or fluorenylmethylaminocarbonyl compound. In some embodiments, the linker is a cleavable linker. For example, a cleavable linker can be one that is released by a bio-labile or enzymatic function, which may or may not be engineered. In some embodiments, the linker is a non- cleavable linker. For example, a non-cleavable linker can be one that is released upon degradation of the macromolecular moiety. [0071] As used herein, term “EC 50 ” refers to a dosage, concentration, or amount of a particular test compound that elicits a dose-dependent response at 50% of maximal expression of a particular response that is induced, provoked, or potentiated by the particular test compound. [0072] As used herein, and unless otherwise specified, the term “IC50” refers to an amount, concentration, or dosage of a particular test compound that achieves a 50% inhibition of a maximal response in an assay that measures such response. [0073] As used herein, the terms “subject” and “patient” are used interchangeably. The terms “subject” and “subjects” refer to an animal, such as a mammal including a non-primate (e.g., a cow, pig, horse, cat, dog, rat, and mouse) and a primate (e.g., a monkey, such as a cynomolgous monkey, a chimpanzee, and a human), and in certain embodiments, a human. In certain embodiments, the subject is a farm animal (e.g., a horse, a cow, a pig, etc.) or a pet (e.g., a dog or a cat). In certain embodiments, the subject is a human. [0074] As used herein, the terms “therapeutic agent” and “therapeutic agents” refer to any agent(s) which can be used in the treatment or prevention of a disorder or one or more symptoms thereof. In certain embodiments, the term “therapeutic agent” includes a compound or conjugate provided herein. In certain embodiments, a therapeutic agent is an agent which is known to be useful for, or has been or is currently being used for the treatment or prevention of a disorder or one or more symptoms thereof. [0075] “Therapeutically effective amount” refers to an amount of a compound or composition that, when administered to a subject for treating a condition, is sufficient to effect such treatment for the condition. A “therapeutically effective amount” can vary depending on, inter alia, the compound, the disease or disorder and its severity, and the age, weight, etc., of the subject to be treated. [0076] “Treating” or “treatment” of any disease or disorder refers, in certain embodiments, to ameliorating a disease or disorder that exists in a subject. In another embodiment, “treating” or “treatment” includes ameliorating at least one physical parameter, which may be indiscernible by the subject. In yet another embodiment, “treating” or “treatment” includes modulating the disease or disorder, either physically (e.g., stabilization of a discernible symptom) or physiologically (e.g., stabilization of a physical parameter) or both. In yet another embodiment, “treating” or “treatment” includes delaying or preventing the onset of the disease or disorder, or delaying or preventing recurrence of the disease or disorder. In yet another embodiment, “treating” or “treatment” includes the reduction or elimination of either the disease or disorder, or retarding the progression of the disease or disorder or of one or more symptoms of the disease or disorder, or reducing the severity of the disease or disorder or of one or more symptoms of the disease or disorder. [0077] As used herein, the term “inhibits growth” (e.g., referring to cells, such as tumor cells) is intended to include any measurable decrease in cell growth (e.g., tumor cell growth) when contacted with a compound or conjugate herein, as compared to the growth of the same cells not in contact with the compound or conjugate herein. In some embodiments, growth may be inhibited by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99%, or 100%. The decrease in cell growth can occur via a variety of mechanisms, including but not limited to, conjugate or compound internalization, apoptosis, necrosis, and/or effector function- mediated activity. [0078] As used herein, the terms “prophylactic agent” and “prophylactic agents” as used refer to any agent(s) which can be used in the prevention of a disorder or one or more symptoms thereof. In certain embodiments, the term “prophylactic agent” includes a compound or conjugate provided herein. In certain other embodiments, the term “prophylactic agent” does not refer a compound or conjugate provided herein. For example, a prophylactic agent is an agent which is known to be useful for, or has been or is currently being used to prevent or impede the onset, development, progression, and/or severity of a disorder. [0079] As used herein, the phrase “prophylactically effective amount” refers to the amount of a therapy (e.g., prophylactic agent) which is sufficient to result in the prevention or reduction of the development, recurrence, or onset of one or more symptoms associated with a disorder or to enhance or improve the prophylactic effect(s) of another therapy (e.g., another prophylactic agent). [0080] In some chemical structures illustrated herein, certain substituents, chemical groups, and atoms are depicted with a curvy/wavy/wiggly line (e.g., that intersects a bond or bonds to indicate the atom through which the substituents, chemical groups, and atoms are bonded. For example, in some structures, such as but not limited to, , or , this curvy/wavy/wiggly line indicates the atoms in the backbone of a conjugate, linker-fluorenylmethoxycarbonyl, or linker-fluorenylmethaminocarbonyl compound structure to which the illustrated chemical entity is bonded. In some structures, such as but not limited t , this curvy/wavy/wiggly line indicates the atoms in the macromolecule as well as the atoms in the backbone of a conjugate, linker- fluorenylmethoxycarbonyl, or linker-fluorenylmethoxycarbonyl compound structure to which the illustrated chemical entity is bonded. [0081] As used herein, illustrations showing substituents bonded to a cyclic group (e.g., aromatic, heteroaromatic, fused ring, and saturated or unsaturated cycloalkyl or heterocycloalkyl) through a bond between ring atoms are meant to indicate, unless specified otherwise, that the cyclic group may be substituted with that substituent at any ring position in the cyclic group or on any ring in the fused ring group, according to techniques set forth herein or which are known in the field to which the instant disclosure pertains. For example, the g wherein subscript q is an integer from zero to four and in which the positions of substituent R 1 are described generically, i.e., not directly attached to any vertex of the bond line structure, i.e., specific ring carbon atom, includes the following, non-limiting examples of groups in which the substituent R 1 is bonded to a specific ring carbon a , , [0082] The term “site-specific” refers to a modification of a polypeptide at a predetermined sequence location in the polypeptide. The modification is at a single, predictable residue of the polypeptide with little or no variation. In particular embodiments, a modified amino acid is introduced at that sequence location, for instance recombinantly or synthetically. Similarly, a moiety can be “site-specifically” linked to a residue at a particular sequence location in the polypeptide. In certain embodiments, a polypeptide can comprise more than one site-specific modification. Compounds of Formulae (I), (II), (III), (IV), (X), (XII), (XIII) and (XIV) [0083] Provided herein are fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl compounds useful for modulating one or more properties of a macromolecule. The fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl compounds can be formed as described herein and used for forming a conjugate with one or more macromolecules. The conjugates can be useful for therapy or diagnosis. In certain embodiments, therapy is the treatment of a cancer or an inflammatory disease or condition. [0084] The embodiments described herein include the recited compounds as well as a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, tautomer, and/or mixture thereof. [0085] In certain embodiments, provided is a compound of Formula (I) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof; wherein RG is a reactive group; POLY is a water soluble polymer; X is a bond, -O-, or -N(R 2 )-; each L 1 and L 2 is, independently, a linker; each R 1 is an electron withdrawing group; R 2 is H or lower alkyl; and n is an integer selected from one to four. In certain embodiments, X is -O- or -N(R 2 )- . In certain embodiments, X is -O-. In certain embodiments, X is -N(R 2 )-. In certain embodiments, n is one. In certain embodiments, n is two. In certain embodiments, n is three. In certain embodiments, n is four. In certain embodiments, n1 is one. In certain embodiments, n1 is two. In certain embodiments, n1 is three. In certain embodiments, n1 is four. [0086] In certain embodiments, provided is a compound of Formula (I) or (X), wherein either L 1 comprises a carbonyl carbon covalently bound to the fluorene, or R 1 comprises an electron withdrawing group, or both. By way of example, in one embodiment, when L 1 comprises a carbonyl carbon covalently bound to the fluorine, then R 1 is independently hydrogen, an electron donating group, or an electron withdrawing group. By way of further example, in one embodiment, when R 1 comprises an electron withdrawing group, then L 1 is a linker. By way of further example, in one embodiment, when L 1 comprises a carbonyl carbon covalently bound to the fluorine, then R 1 comprises an electron withdrawing group. [0087] In certain embodiments, the compound of Formula (I) is according to Formula (II) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof

wherein RG, POLY, X, L 2 , and R 1 are as defined in the Summary, or in any embodiment herein. [0088] In certain embodiments, the compound of Formula (I) is according to Formula (III) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof wherein POLY and R 1 are as defined in the Summary, or in any embodiment herein, and p is an integer selected from one to eight. In certain embodiments, p is one. In certain embodiments, p is two. In certain embodiments, p is three. In certain embodiments, p is four. In certain embodiments, p is five. In certain embodiments, p is six. In certain embodiments, p is seven. In certain embodiments, p is eight. [0089] In certain embodiments, the compound of Formula (I) is according to Formula (IV) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof wherein POLY and R 1 are as defined in the Summary, or in any embodiment herein, and p is an integer selected from one to eight. In certain embodiments, p is one. In certain embodiments, p is two. In certain embodiments, p is three. In certain embodiments, p is four. In certain embodiments, p is five. In certain embodiments, p is six. In certain embodiments, p is seven. In certain embodiments, p is eight. [0090] In certain embodiments, the compound of Formula (I) is according to Formula (IV) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof wherein POLY and R 1 are as defined in the Summary, or in any embodiment herein, and p is an integer selected from one to eight. In certain embodiments, p is one. In certain embodiments, p is two. In certain embodiments, p is three. In certain embodiments, p is four. In certain embodiments, p is five. In certain embodiments, p is six. In certain embodiments, p is seven. In certain embodiments, p is eight. [0091] In certain embodiments, provided is a compound of Formula (X) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof; wherein RG is a reactive group; POLY is a water soluble polymer; X is a bond, -O-, or -N(R 2 )-; each of L 1 , L 2 , and L 3 is, independently, a linker; each R 1 is an electron withdrawing group; R 2 is H or lower alkyl; m is an integer selected from zero to four. In certain embodiments, X is -O- or -N(R 2 )-. In certain embodiments, X is -O-. In certain embodiments, X is -N(R 2 )-. In certain embodiments, m is zero. In certain embodiments, m is one. In certain embodiments, m is two. In certain embodiments, m is three. In certain embodiments, m is four. In certain embodiments, m1 is one. In certain embodiments, m1 is two. In certain embodiments, m1 is three. In certain embodiments, m1 is four. In certain embodiments, m2 is one. In certain embodiments, m2 is two. In certain embodiments, m2 is three. In certain embodiments, m2 is four. [0092] In certain embodiments, the compound of Formula (X) is according to Formula (XII) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof wherein RG, POLY, X, L 2 , L 3 , and R 4 are as defined in the Summary, or in any embodiment herein. [0093] In certain embodiments, the compound of Formula (X) is according to Formula (XIII) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof wherein POLY and R 4 are as defined in the Summary, or in any embodiment herein, and p is an integer selected from one to eight. In certain embodiments, p is one. In certain embodiments, p is two. In certain embodiments, p is three. In certain embodiments, p is four. In certain embodiments, p is five. In certain embodiments, p is six. In certain embodiments, p is seven. In certain embodiments, p is eight. [0094] In certain embodiments, the compound of Formula (X) is according to Formula (XIV) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof

wherein POLY and R 4 are as defined in the Summary, or in any embodiment herein, and p is an integer selected from one to eight. In certain embodiments, p is one. In certain embodiments, p is two. In certain embodiments, p is three. In certain embodiments, p is four. In certain embodiments, p is five. In certain embodiments, p is six. In certain embodiments, p is seven. In certain embodiments, p is eight. [0095] In certain embodiments, each linker L 1 , L 2 , and L 3 can be any linker deemed suitable by a person of skill in the art. In certain embodiments, provided is a compound of Formula (I) or (X), wherein L 1 includes an ester wherein the carbonyl carbon of the ester functional group is covalently bound to the fluorene. In certain embodiments, provided is a compound of Formula (I) or (X), wherein L 1 includes a ketone wherein the carbonyl carbon of the ketone functional group is covalently bound to the fluorene. In certain embodiments, provided is a compound of Formula (I) or (X), wherein L 1 includes an anhydride wherein one of the carbonyls of the anhydride functional group is covalently bound to the fluorene. In certain embodiments, provided is a compound of Formula (I) or (X), wherein L 1 includes a sulfonyl wherein the sulfur of the sulfonyl functional group is covalently bound to the fluorene. In certain embodiments, provided is a compound of Formula (I) or (X), wherein L 1 includes an ammonium where the positively charged nitrogen of the ammonium functional group is covalently bound to the fluorene. In certain embodiments, provided is a compound of Formula (I) or (X), wherein L 1 is -X 1 -C1-6alkylene-X 2 -C(O)- wherein X 1 and X 2 are independently selected from the group consisting of -O-, -S- or -N(R 2 )-, R 2 is hydrogen or lower alkyl, and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is selected from the group consisting of -O-C 1-6 alkylene-S-C(O)-, -O-C 1-6 alkylene-NH-C(O)-, -S-C1-6alkylene-O-C(O)-, -S-C1-6alkylene-NH-C(O)-, -NH-C1-6alkylene-O-C(O)-, -NH-C 1-6 alkylene-S-C(O)-, -O-C 1-6 alkylene-N(Me)-C(O)-, -S-C 1-6 alkylene-N(Me)-C(O)-, -N(Me)-C1-6alkylene-O-C(O)-, -N(Me)-C1-6alkylene-S-C(O)-, -O-C1-6alkylene-N(Et)-C(O)-, -S-C 1-6 alkylene-N(Et)-C(O)-, -N(Et)-C 1-6 alkylene-O-C(O)-, and -N(Et)-C 1-6 alkylene-S-C(O)- ; and each -C1-6alkylene- is independently optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -O-C 1-6 alkylene-S-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -O-C1-6alkylene-NH-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -S-C 1-6 alkylene-O-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -S-C1-6alkylene-NH-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -NH-C1-6alkylene-O-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -NH-C 1-6 alkylene-S-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -O-C1-6alkylene-N(Me)-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -S-C 1-6 alkylene-N(Me)-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -N(Me)-C1-6alkylene-O-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -N(Me)-C 1-6 alkylene-S-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -O-C 1-6 alkylene-N(Et)-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -S-C1-6alkylene-N(Et)-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -N(Et)-C 1-6 alkylene-O-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -N(Et)-C1-6alkylene-S-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In certain embodiments, provided is a compound of Formula (I) or (X), wherein L 1 is -O-CH2-CH2-N(H)-C(O)- wherein the carbonyl carbon is covalently bound to the fluorene. [0096] In certain embodiments, provided is a compound of Formula (I), (II), or (X), wherein L 2 is lower alkylene, -CH 2 -, -CH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 -, or -CH 2 -CH 2 -C(O)-. In certain embodiments, provided is a compound of Formula (I), (II), or (X), wherein L 2 is lower alkylene selected from the group consisting of -CH 2 -, -CH 2 CH 2 -, -CH 2 CH 2 CH 2 -, -CH 2 CH 2 CH 2 CH 2 - , -CH2CH2CH2CH2CH2-, and -CH2CH2CH2CH2CH2CH2- wherein each are independently optionally substituted with one, two, or three groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH2- optionally substituted with a group selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH 2 CH 2 - independently optionally substituted with one or two groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH 2 CH 2 CH 2 - independently optionally substituted with one, two, or three groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH2CH2CH2CH2- independently optionally substituted with one, two, or three groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH2CH2CH2CH2CH2- independently optionally substituted with one, two, or three groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH2CH2CH2CH2CH2CH2- independently optionally substituted with one, two, or three groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In certain embodiments, provided is a compound of Formula (I), (II), or (X), wherein L 2 is -CH 2 -. In certain embodiments, provided is a compound of Formula (I), (II), or (X), wherein L 2 is -CH2CH2OCH2CH2OCH2CH2-. In certain embodiments, provided is a compound of Formula (I), (II), or (X), wherein L 2 is -CH 2 -CH 2 -C(O)-. [0097] In certain embodiments, provided is a compound of Formula (X) or (XII), wherein L 3 is lower alkylene. In certain embodiments, provided is a compound of Formula (X) or (XII), wherein L 3 is -CH2- or -CH2CH2-. In certain embodiments, provided is a compound of Formula (X) or (XII), wherein L 2 is -CH 2 -. In certain embodiments, provided is a compound of Formula (X) or (XII), wherein L 3 is -CH2-CH2-. [0098] In certain embodiments, RG is any reactive group deemed suitable by the person of skill. In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG comprises an azide, alkyne, hydrazide, aldehyde, alkoxyamine, amine or -NR 2 , carboxyl, ester, or maleimide. In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG comprises an azide. In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG comprises a hydrazide. In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG comprises an aldehyde. In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG comprises an alkoxyamine. In one embodiment, the alkoxyamine is -O-NH 2 . In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG comprises an amine. In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG comprises a carboxyl. In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG comprises an ester. In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG comprises a maleimide. In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG comprises an alkyne. In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG comprises a strained alkyne. In certain embodiments, provided is a compound of Formula (I), (II), (X), or (XII), wherein RG is selected from . [0099] In the conjugates described herein, POLY can be any water-soluble polymer deemed useful by a person of skill in the art. Useful polymers are described here, and in the sections below. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), or (XIV), wherein POLY is selected from polyethylene glycol (PEG), polyvinylpyrrolidone, polyglycerol, poly(N-2-hydroxypropyl) methacrylamide, and polyoxazoline. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), or (XIV), wherein POLY is polyethylene glycol (PEG). In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), or (XIV), wherein POLY has a molecular weight from 5 kDa to 50 kDa. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), or (XIV), wherein POLY has a molecular weight from 10 kDa to 25 kDa. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), or (XIV), wherein POLY has a molecular weight of about 20 kDa. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), or (XIV), wherein POLY is PEG having a molecular weight from 5 kDa to 50 kDa. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), or (XIV), wherein POLY is PEG having a molecular weight from 10 kDa to 25 kDa. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), or (XIV), wherein POLY is PEG having a molecular weight of about 20 kDa. In certain embodiments, POLY is uncapped (e.g., terminates with hydroxyl). In certain embodiments, POLY is methoxy-PEG (i.e., terminates with methyl or methoxy). In certain embodiments, PEG is linear. In certain embodiments, PEG is branched. [00100] Provided are compounds of the following formulae 101;

, 105; a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof. [00101] In the formulae above, in certain embodiments, each R 1 is hydrogen, an electron donating group, or an electron withdrawing group. In one embodiment, each R 1 is hydrogen. In one embodiment, each R 1 is an electron donating group. In one embodiment, each R 1 is an electron withdrawing group. The electron donating group can be any electron donating group deemed suitable to the person of skill in the art. The electron withdrawing group can be any electron withdrawing group deemed suitable to the person of skill in the art. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein each R 1 is independently selected from the group consisting of hydrogen, haloalkyl, halogen, -CN, -SO3H, -C(O)R 3 , -C(O)OR 3 , -OR 3 , -N(H)C(O)R 3 , - N(H)CO 2 R 3 , and -N(H)C(O)C(H)(R 3 )CO 2 H wherein each R 3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein each R 1 is independently selected from the group consisting of haloalkyl, halogen, -CN, - SO 3 H, -C(O)R 3 , -C(O)OR 3 , -OR 3 , -N(H)C(O)R 3 , -N(H)CO 2 R 3 , and - N(H)C(O)C(H)(R 3 )CO 2 H wherein each R 3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein each R 1 is independently selected from the group consisting of -H, -CF3, -Br, -Cl, -F, -CN, -SO3H, - C(O)Me, -CO 2 Me, -OMe, -N(H)C(O)Me, -N(H)CO 2 Me, and -N(H)C(O)C(H)(Me)CO 2 H. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein each R 1 is independently selected from the group consisting of -CF3, -Br, -Cl, -F, -CN, -SO3H, -C(O)Me, -CO2Me, -OMe, -N(H)C(O)Me, -N(H)CO2Me, and -N(H)C(O)C(H)(Me)CO 2 H. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compound 101-106, wherein R 1 is -Br. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein R 1 is -Cl. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein R 1 is -F. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein R 1 is -CN. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein R 1 is -SO3H. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein R 1 is -C(O)Me. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein R 1 is -OMe. [00102] In the formulae above, each R 4 is hydrogen or an electron withdrawing group. In one embodiment, each R 4 is hydrogen. In one embodiment, each R 4 is an electron withdrawing group. The electron withdrawing group can be any electron withdrawing group deemed suitable to the person of skill in the art. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein each R 4 is independently selected from the group consisting of -C(O)R 3 , -C(O)OR 3 , and -S(O)2R 3 , wherein each R 3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein each R 4 is independently selected from the group consisting of -C(O)R 3 , -C(O)OR 3 , and -S(O)2R 3 wherein each R 3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein each R 4 is independently selected from the group consisting of hydrogen, -CF 3 , -C(O)Me, - CO2Me, and -S(O)2CH3. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein each R 4 is independently selected from the group consisting of -C(O)Me, and -S(O)2R 3 . In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, wherein R 4 is -C(O)Me. In certain embodiments, provided is a compound of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or (101)-(106)compounds 101-106, wherein R 4 is -S(O)2CH3. Optically Active Compounds [00103] In certain embodiments, compounds provided herein may have several chiral centers and may exist in and be isolated in optically active and racemic forms. In certain embodiments, some compounds may exhibit polymorphism. A person of skill in the art will appreciate that compounds provided herein can exist in any racemic, optically-active, diastereomeric, polymorphic, or stereoisomeric form, and/or mixtures thereof. A person of skill in the art will also appreciate that such compounds described herein that possess the useful properties also described herein is within the scope of this disclosure. A person of skill in the art will further appreciate how to prepare optically active forms of the compounds described herein, for example, by resolution of racemic forms via recrystallization techniques, by synthesis from optically-active starting materials, by chiral synthesis, or by chromatographic separation using a chiral stationary phase. In addition, most amino acids are chiral (i.e., designated as L- or D-, wherein the L- enantiomer is the naturally occurring configuration) and can exist as separate enantiomers. [00104] Examples of methods to obtain optically active materials are known in the art, and include at least the following: i) physical separation of crystals - a technique whereby macroscopic crystals of the individual enantiomers are manually separated. This technique can be used if crystals of the separate enantiomers exist (i.e., the material is a conglomerate, and the crystals are visually distinct); ii) simultaneous crystallization - a technique whereby the individual enantiomers are separately crystallized from a solution of the racemate, only if the latter is a conglomerate in the solid state; iii) enzymatic resolutions - a technique wherein partial or complete separation of a racemate is accomplished by virtue of different rates of reaction of the enantiomers in the presence of an enzyme; iv) enzymatic asymmetric synthesis - a synthetic technique wherein at least one step of the synthesis uses an enzymatic reaction to obtain an enantiomerically pure or enriched synthetic precursor of the desired enantiomer; v) chemical asymmetric synthesis - a synthetic technique wherein the desired enantiomer is synthesized from an achiral precursor using chiral catalysts or chiral auxiliaries to produce asymmetry (i.e., chirality) in the product; vi) diastereomer separations - a technique wherein a racemic compound is treated with an enantiomerically pure reagent (a chiral auxiliary) that converts the individual enantiomers to diastereomers. The resulting diastereomers are then separated by chromatography or crystallization by virtue of their now more distinct diastereomeric differences, and then the chiral auxiliary is removed to obtain each enantiomer; vii) first- and second-order asymmetric transformations - a technique wherein diastereomers of the racemate equilibrate in solution to yield a preponderance of a diastereomer of the desired enantiomer, or where kinetic or thermodynamic crystallization of the diastereomer of the desired enantiomer perturbs the equilibrium such that eventually in principle all the material is converted to the crystalline diastereomer of the desired enantiomer. The desired enantiomer is then derived from the diastereomer; viii) kinetic resolutions - this technique refers to the achievement of partial or complete resolution of a racemate (or of a further resolution of a partially resolved compound) by virtue of unequal reaction rates of the enantiomers with a chiral or non-racemic reagent or catalyst under kinetic conditions; ix) enantiospecific synthesis from non-racemic precursors - a synthetic technique wherein the desired enantiomer is obtained from chiral starting materials and where the stereochemical integrity is not or is only minimally compromised over the course of the synthesis; x) chiral liquid chromatography - a technique wherein the enantiomers of a racemate are separated in a liquid mobile phase by virtue of their different interactions with a stationary phase. The stationary phase can be made of chiral material or the mobile phase can contain an additional chiral material to provoke the different interactions; xi) chiral gas chromatography - a technique wherein the racemate is volatilized and enantiomers are separated by virtue of their different interactions in the gaseous mobile phase with a column containing a fixed non-racemic adsorbent phase; xii) extraction with chiral solvents - a technique wherein the enantiomers are separated by virtue of kinetic or thermodynamic dissolution of one enantiomer into a particular chiral solvent; xiii) transport across chiral membranes - a technique wherein a racemate is placed in contact with a thin membrane barrier. The barrier typically separates two miscible fluids, one containing the racemate, and a driving force such as a concentration or pressure differential causes preferential transport across the membrane barrier. Separation occurs as a result of the non-racemic nature of the membrane which allows only one enantiomer of the racemate to pass through. [00105] In some embodiments, provided herein are compositions of compounds of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, that are substantially free of a designated stereoisomer of that compound. In certain embodiments, in the methods and compounds of this disclosure, the compounds are substantially free of other stereoisomers. In some embodiments, the composition includes a compound that is at least 85%, 90%, 95%, 98%, or 99% to 100% by weight of the compound, the remainder comprising other chemical species or enantiomers. In some embodiments, provided herein are compositions of compounds of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106, that are substantially free of a designated enantiomer of that compound. In certain embodiments, in the methods and compounds of this disclosure, the compounds are substantially free of other enantiomers. In some embodiments, the composition includes a compound that is at least 85%, 90%, 95%, 98%, or 99% to 100% by weight of the compound, the remainder comprising other chemical species or enantiomers. Isotopically Enriched Compounds [00106] Also provided herein are isotopically enriched compounds including, but not limited to, isotopically enriched compounds of Formula (I)-(IV), (X), (XII), (XIII), (XIV), or compounds 101-106. [00107] Isotopic enrichment (for example, deuteration) of pharmaceuticals to improve pharmacokinetics (“PK”), pharmacodynamics (“PD”), and/or toxicity profiles, has been previously demonstrated within some classes of drugs. See, for example, Lijinsky et al., Food Cosmet. Toxicol., 20: 393 (1982); Lijinsky et al., J. Nat. Cancer Inst., 69: 1127 (1982); Mangold et al., Mutation Res. 308: 33 (1994); Gordon et al., Drug Metab. Dispos., 15: 589 (1987); Zello et al., Metabolism, 43: 487 (1994); Gately et al., J. Nucl. Med., 27: 388 (1986); Wade D, Chem. Biol. Interact.117: 191 (1999). [00108] Isotopic enrichment of a drug can be used, for example, to (1) reduce or eliminate unwanted metabolites; (2) increase the half-life of the parent drug; (3) decrease the number of doses needed to achieve a desired effect; (4) decrease the amount of a dose necessary to achieve a desired effect; (5) increase the formation of active metabolites, if any are formed; and/or (6) decrease the production of deleterious metabolites in specific tissues. Isotopic enrichment of a drug can also be used to create a more effective and/or safer drug for combination therapy, whether the combination therapy is intentional or not. [00109] Replacement of an atom for one of its isotopes often will result in a change in the reaction rate of a chemical reaction. This phenomenon is known as the Kinetic Isotope Effect (“KIE”). For example, if a C–H bond is broken during a rate-determining step in a chemical reaction (i.e., the step with the highest transition state energy), substitution of a (heavier) isotope for that reactive hydrogen will cause a decrease in the reaction rate. The Deuterium Kinetic Isotope Effect (“DKIE”) is the most common form of KIE. (See, e.g., Foster et al., Adv. Drug Res., vol. 14, pp. 1-36 (1985); Kushner et al., Can. J. Physiol. Pharmacol., vol. 77, pp.79-88 (1999)). [00110] The magnitude of the DKIE can be expressed as the ratio between the rates of a given reaction in which a C–H bond is broken, and the same reaction where deuterium is substituted for hydrogen and the C–D bond is broken. The DKIE can range from about one (no isotope effect) to very large numbers, such as 50 or more, meaning that the reaction can be fifty, or more, times slower when deuterium has been substituted for hydrogen. [00111] Substitution of tritium (“T”) for hydrogen results in yet a stronger bond than deuterium and gives numerically larger isotope effects. Similarly, substitution of isotopes for other elements including, but not limited to, 13 C or 14 C for carbon; 33 S, 34 S, or 36 S for sulfur; 15 N for nitrogen; and 17 O or 18 O for oxygen may lead to a similar kinetic isotope effect. [00112] The animal body expresses a variety of enzymes for the purpose of eliminating foreign substances, such as therapeutic agents, from its circulation system. Examples of such enzymes include the cytochrome P450 enzymes (“CYPs”), esterases, proteases, reductases, dehydrogenases, and monoamine oxidases to react with and convert these foreign substances to more polar intermediates or metabolites for renal excretion. Some of the most common metabolic reactions of pharmaceutical compounds involve the oxidation of a carbon-hydrogen (C–H) bond to either a carbon-oxygen (C–O) or carbon-carbon (C=C) pi-bond. The resultant metabolites may be stable or unstable under physiological conditions, and can have substantially different PK/PD, and acute and long-term toxicity profiles relative to the parent compounds. For many drugs, such oxidations are rapid. Therefore, these drugs often require the administration of multiple or high daily doses. [00113] Therefore, isotopic enrichment at certain positions of a compound provided herein will produce a detectable KIE that will affect the pharmacologic, PK, PD, and/or toxicological profiles of a compound provided herein in comparison with a similar compound having a natural isotopic composition. Conjugates [00114] Provided herein are conjugates of macromolecules with one of the fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl compounds described herein. The conjugates are covalently linked directly or indirectly, via a linker. In certain embodiments, a conjugate comprises a macromolecule conjugated to one or more fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl compounds described herein. In certain embodiments, a conjugate comprises more than one fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl group. In certain embodiments, conjugate comprises more than one macromolecule. In certain embodiments, the macromolecule is linked to one fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl group. In further embodiments, the macromolecule is linked to more than one fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl compounds. In certain embodiments, the macromolecule is linked to two, three, four, five, six, seven, eight, or more fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl groups. [00115] The linker can be any linker capable of forming at least one bond to the macromolecule and at least one bond to a fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl compound. Useful linkers are described in the sections and examples herein and in particular, below. [00116] The macromolecule can be any macromolecule deemed suitable by the person of skill in the art. In certain embodiments, the macromolecule is a protein, peptide, antibody or antigen-binding fragment thereof, nucleic acid, carbohydrate, or other large molecule composed of polymerized monomers. In certain embodiments, the macromolecule is a peptide of two or more residues. In certain embodiments, the macromolecule is a peptide of ten or more residues. In certain embodiments, the macromolecule is at least 1000 Da in mass. In certain embodiments, the macromolecule comprises at least 1000 atoms. Useful macromolecules are described in the sections below. [00117] In certain embodiments, provided is a conjugate of Formula (I′) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers, regioisomer, and/or mixture of regioisomers thereof wherein PRO is a macromolecule; w is an integer selected from one to ten; each RG′ is independently a divalent residue of a reactive group; each POLY is independently a water soluble polymer; each X is independently a bond, -O-, or -N(R 2 )-; each L 1 and L 2 is, independently, a linker; each R 1 is independently an electron withdrawing group; each R 2 is independently H or lower alkyl; and each n is independently an integer selected from one to four. In certain embodiments, each X is independently -O- or -N(R 2 )-. In certain embodiments, each X is independently -O-. In certain embodiments, each X is independently -N(R 2 )-. In certain embodiments, each n is one. In certain embodiments, each n is two. In certain embodiments, each n is three. In certain embodiments, each n is four. In certain embodiments, n1 is one. In certain embodiments, n1 is two. In certain embodiments, n1 is three. In certain embodiments, n1 is four. In certain embodiments, w is one. In certain embodiments, w is two. In certain embodiments, w is three. In certain embodiments, w is four. In certain embodiments, w is five. In certain embodiments, w is six. In certain embodiments, w is seven. In certain embodiments, w is eight. In certain embodiments, w is nine. In certain embodiments, w is ten. [00118] In certain embodiments, provided is a conjugate of Formula (I′) or (X′), wherein either L 1 comprises a carbonyl carbon covalently bound to the fluorene, or R 1 comprises an electron withdrawing group, or both. By way of example, in one embodiment, when L 1 comprises a carbonyl carbon covalently bound to the fluorine, then R 1 is independently hydrogen, an electron donating group, or an electron withdrawing group. By way of further example, in one embodiment, when R 1 comprises an electron withdrawing group, then L 1 is a linker. By way of further example, in one embodiment, when L 1 comprises a carbonyl carbon covalently bound to the fluorine, then R 1 comprises an electron withdrawing group. [00119] In certain embodiments, the conjugate of Formula (I′) is according to Formula (II′) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers, regioisomer, and/or mixture of regioisomers thereof wherein PRO, w, RG′, POLY, X, and R 1 are as defined in the Summary, or in any embodiment herein. In certain embodiments, w is one. In certain embodiments, w is two. In certain embodiments, w is three. In certain embodiments, w is four. In certain embodiments, w is five. In certain embodiments, w is six. In certain embodiments, w is seven. In certain embodiments, w is eight. In certain embodiments, w is nine. In certain embodiments, w is ten. [00120] In certain embodiments, the conjugate of Formula (I′) is according to Formula (III′) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers, regioisomer, and/or mixture of regioisomers thereof

wherein PRO, w, POLY, and R 1 are as defined in the Summary, or in any embodiment herein, and each p is independently an integer selected from one to eight. In certain embodiments, PRO is bound to a nitrogen of the triazole that is other than the middle nitrogen of the triazole. Accordingly, in certain embodiments, the triazole formation provides one of two possible regioisomeric products. In one regioisomeric embodiment, PRO is bound to a nitrogen shown below . In one regioisomeric embodiment, PRO is bound to a nitrogen shown below . In certain embodiments, p is one. In certain embodiments, p is two. In certain embodiments, p is three. In certain embodiments, p is four. In certain embodiments, p is five. In certain embodiments, p is six. In certain embodiments, p is seven. In certain embodiments, p is eight. In certain embodiments, w is one. In certain embodiments, w is two. In certain embodiments, w is three. In certain embodiments, w is four. In certain embodiments, w is five. In certain embodiments, w is six. In certain embodiments, w is seven. In certain embodiments, w is eight. In certain embodiments, w is nine. In certain embodiments, w is ten. [00121] In certain embodiments, the conjugate of Formula (I′) is according to Formula (IV′) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers, regioisomer, and/or mixture of regioisomers thereof wherein PRO, w, POLY, and R 1 are as defined in the Summary, or in any embodiment herein, and each p is independently an integer selected from one to eight. In certain embodiments, PRO is bound to a nitrogen of the triazole that is other than the middle nitrogen of the triazole. Accordingly, in certain embodiments, the triazole formation provides one of two possible regioisomeric products. In one regioisomeric embodiment, PRO is bound to a nitrogen shown below . In one regioisomeric embodiment, PRO is bound to a nitrogen shown below

. In certain embodiments, p is one. In certain embodiments, p is two. In certain embodiments, p is three. In certain embodiments, p is four. In certain embodiments, p is five. In certain embodiments, p is six. In certain embodiments, p is seven. In certain embodiments, p is eight. In certain embodiments, w is one. In certain embodiments, w is two. In certain embodiments, w is three. In certain embodiments, w is four. In certain embodiments, w is five. In certain embodiments, w is six. In certain embodiments, w is seven. In certain embodiments, w is eight. In certain embodiments, w is nine. In certain embodiments, w is ten. [00122] In certain embodiments, the conjugate of Formula (I′) is according to Formula (V′) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers, regioisomer, and/or mixture of regioisomers thereof wherein PRO, w, POLY, and R 1 are as defined in the Summary, or in any embodiment herein, and each p is independently an integer selected from one to eight. In certain embodiments, p is one. In certain embodiments, p is two. In certain embodiments, p is three. In certain embodiments, p is four. In certain embodiments, p is five. In certain embodiments, p is six. In certain embodiments, p is seven. In certain embodiments, p is eight. In certain embodiments, w is one. In certain embodiments, w is two. In certain embodiments, w is three. In certain embodiments, w is four. In certain embodiments, w is five. In certain embodiments, w is six. In certain embodiments, w is seven. In certain embodiments, w is eight. In certain embodiments, w is nine. In certain embodiments, w is ten. [00123] In certain embodiments, provided is a conjugate of Formula (X′) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers, regioisomer, and/or mixture of regioisomers thereof wherein PRO is a macromolecule; w is an integer selected from one to ten; each RG′ is independently a divalent residue of a reactive group; each POLY is independently a water soluble polymer; each X is independently a bond, -O-, or -N(R 2 )-; each L 1 , L 2 , and L 3 is, independently, a linker; each R 1 is independently an electron withdrawing group; each R 2 is independently H or lower alkyl; and each m is independently an integer selected from one to four. In certain embodiments, each X is independently -O- or -N(R 2 )-. In certain embodiments, each X is independently -O-. In certain embodiments, each X is independently -N(R 2 )-. In certain embodiments, m is one. In certain embodiments, m is two. In certain embodiments, m is three. In certain embodiments, m is four. In certain embodiments, m1 is one. In certain embodiments, m1 is two. In certain embodiments, m1 is three. In certain embodiments, m1 is four. In certain embodiments, w is one. In certain embodiments, w is two. In certain embodiments, w is three. In certain embodiments, w is four. In certain embodiments, w is five. In certain embodiments, w is six. In certain embodiments, w is seven. In certain embodiments, w is eight. In certain embodiments, w is nine. In certain embodiments, w is ten. [00124] In certain embodiments, the conjugate of Formula (X′) is according to Formula (XII′) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers, regioisomer, and/or mixture of regioisomers thereof

wherein PRO, w, RG′, POLY, X, L 2 , L 3 , and R 4 are as defined in the Summary, or in any embodiment herein. In certain embodiments, w is one. In certain embodiments, w is two. In certain embodiments, w is three. In certain embodiments, w is four. In certain embodiments, w is five. In certain embodiments, w is six. In certain embodiments, w is seven. In certain embodiments, w is eight. In certain embodiments, w is nine. In certain embodiments, w is ten. [00125] In certain embodiments, the conjugate of Formula (X′) is according to Formula (XIII′) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers, regioisomer, and/or mixture of regioisomers thereof wherein PRO, w, POLY, and R 4 are as defined in the Summary, or in any embodiment herein, and p is independently an integer selected from one to eight. In certain embodiments, PRO is bound to a nitrogen of the triazole that is other than the middle nitrogen of the triazole. Accordingly, in certain embodiments, the triazole formation provides one of two possible regioisomeric products. In one regioisomeric embodiment, PRO is bound to a nitrogen shown below . In one regioisomeric embodiment, PRO is bound to a nitrogen shown below . In certain embodiments, p is one. In certain embodiments, p is two. In certain embodiments, p is three. In certain embodiments, p is four. In certain embodiments, p is five. In certain embodiments, p is six. In certain embodiments, p is seven. In certain embodiments, p is eight. In certain embodiments, w is one. In certain embodiments, w is two. In certain embodiments, w is three. In certain embodiments, w is four. In certain embodiments, w is five. In certain embodiments, w is six. In certain embodiments, w is seven. In certain embodiments, w is eight. In certain embodiments, w is nine. In certain embodiments, w is ten. [00126] In certain embodiments, the conjugate of Formula (X′) is according to Formula (XIV′) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers, regioisomer, and/or mixture of regioisomers thereof wherein PRO, w, POLY, and R 4 are as defined in the Summary, or in any embodiment herein, and p is independently an integer selected from one to eight. In certain embodiments, PRO is bound to a nitrogen of the triazole that is other than the middle nitrogen of the triazole. Accordingly, in certain embodiments, the triazole formation provides one of two possible regioisomeric products. In one regioisomeric embodiment, PRO is bound to a nitrogen shown below

. In one regioisomeric embodiment, PRO is bound to a nitrogen shown below . In certain embodiments, p is one. In certain embodiments, p is two. In certain embodiments, p is three. In certain embodiments, p is four. In certain embodiments, p is five. In certain embodiments, p is six. In certain embodiments, p is seven. In certain embodiments, p is eight. In certain embodiments, w is one. In certain embodiments, w is two. In certain embodiments, w is three. In certain embodiments, w is four. In certain embodiments, w is five. In certain embodiments, w is six. In certain embodiments, w is seven. In certain embodiments, w is eight. In certain embodiments, w is nine. In certain embodiments, w is ten. [00127] In certain embodiments, the conjugate of Formula (X′) is according to Formula (XV′) or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers, regioisomer, and/or mixture of regioisomers thereof (XV′) wherein PRO, w, POLY, and R 4 are as defined in the Summary, or in any embodiment herein, and p is independently an integer selected from one to eight. In certain embodiments, p is one. In certain embodiments, p is two. In certain embodiments, p is three. In certain embodiments, p is four. In certain embodiments, p is five. In certain embodiments, p is six. In certain embodiments, p is seven. In certain embodiments, p is eight. In certain embodiments, w is one. In certain embodiments, w is two. In certain embodiments, w is three. In certain embodiments, w is four. In certain embodiments, w is five. In certain embodiments, w is six. In certain embodiments, w is seven. In certain embodiments, w is eight. In certain embodiments, w is nine. In certain embodiments, w is ten. [00128] In certain embodiments, each linker L 1 , L 2 , and L 3 can be any linker deemed suitable by the practitioner of skill in the art. In certain embodiments, provided is a conjugate of Formula (I′) or (X′), wherein L 1 includes an ester wherein the carbonyl carbon of the ester functional group is covalently bound to the fluorene. In certain embodiments, provided is a conjugate of Formula (I′) or (X′), wherein L 1 includes a ketone wherein the carbonyl carbon of the ketone functional group is covalently bound to the fluorene. In certain embodiments, provided is a conjugate of Formula (I′) or (X′), wherein L 1 includes an anhydride wherein one of the carbonyls of the anhydride functional group is covalently bound to the fluorene. In certain embodiments, provided is a conjugate of Formula (I′) or (X′), wherein L 1 includes a sulfonyl wherein the sulfur of the sulfonyl functional group is covalently bound to the fluorene. In certain embodiments, provided is a conjugate of Formula (I′) or (X′), wherein L 1 includes an ammonium where the positively charged nitrogen of the ammonium functional group is covalently bound to the fluorene. In certain embodiments, provided is a compound of Formula (I′) or (X′), wherein L 1 is -X 1 -C1-6alkylene-X 2 -C(O)- wherein X 1 and X 2 are independently selected from the group consisting of -O-, -S- or -N(R 2 )-, R 2 is hydrogen or lower alkyl, and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is selected from the group consisting of -O-C 1-6 alkylene-S-C(O)-, -O-C 1-6 alkylene-NH-C(O)-, -S-C1-6alkylene-O-C(O)-, -S-C1-6alkylene-NH-C(O)-, -NH-C1-6alkylene-O-C(O)-, -NH-C 1-6 alkylene-S-C(O)-, -O-C 1-6 alkylene-N(Me)-C(O)-, -S-C 1-6 alkylene-N(Me)-C(O)-, -N(Me)-C1-6alkylene-O-C(O)-, -N(Me)-C1-6alkylene-S-C(O)-, -O-C1-6alkylene-N(Et)-C(O)-, -S-C 1-6 alkylene-N(Et)-C(O)-, -N(Et)-C 1-6 alkylene-O-C(O)-, and -N(Et)-C 1-6 alkylene-S-C(O)- ; and each -C1-6alkylene- is independently optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -O-C1-6alkylene-S-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -O-C 1-6 alkylene-NH-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -S-C1-6alkylene-O-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -S-C 1-6 alkylene-NH-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -NH-C1-6alkylene-O-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -NH-C1-6alkylene-S-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -O-C 1-6 alkylene-N(Me)-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -S-C1-6alkylene-N(Me)-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -N(Me)-C 1-6 alkylene-O-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -N(Me)-C1-6alkylene-S-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -O-C 1-6 alkylene-N(Et)-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -S-C 1-6 alkylene-N(Et)-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -N(Et)-C1-6alkylene-O-C(O)- and -C1-6alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 1 is -N(Et)-C 1-6 alkylene-S-C(O)- and -C 1-6 alkylene- is optionally substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, provided is a conjugate of Formula (I′) or (X′), wherein each L 1 is independently -O-CH 2 -CH 2 -N(H)-C(O)- wherein the carbonyl carbon is covalently bound to the fluorene. [00129] In certain embodiments, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each L 2 is independently lower alkylene, -CH2-, -CH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 -, or -CH 2 -CH 2 -C(O)-. In one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each L 2 is independently lower alkylene selected from the group consisting of -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2- , -CH 2 CH 2 CH 2 CH 2 CH 2 -, and -CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 - wherein each are independently optionally substituted with one, two, or three groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH 2 - optionally substituted with a group selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH 2 CH 2 - independently optionally substituted with one or two groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH 2 CH 2 CH 2 - independently optionally substituted with one, two, or three groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH2CH2CH2CH2- independently optionally substituted with one, two, or three groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH2CH2CH2CH2CH2- independently optionally substituted with one, two, or three groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, L 2 is -CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 - independently optionally substituted with one, two, or three groups independently selected from a halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each L 2 is -CH 2 -. . In one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each L 2 is -CH2CH2OCH2CH2OCH2CH2-. In one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each L 2 is -CH 2 -CH 2 - C(O)-. [00130] In one embodiment, provided is a conjugate of Formula (X′) or (XII′), (XIII′), or (XIV′), wherein each L 3 is independently lower alkylene. In certain embodiments, provided is a conjugate of Formula (X′) or (XII′), wherein each L 3 is independently -CH 2 - or -CH 2 CH 2 - . In one embodiment, provided is a conjugate of Formula (X′) or (XII′), wherein each L 3 is -CH 2 -. In one embodiment, provided is a conjugate of Formula (X′) or (XII′), wherein each L 3 is -CH2-CH2-. [00131] In certain embodiments, each RG′ is independently a divalent residue of any reactive group RG deemed suitable by the person of skill in the art. In certain embodiments, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each RG′ is independently a divalent residue of RG where RG comprises an azide, alkyne, hydrazide, aldehyde, alkoxyamine, amine, carboxyl, ester, or maleimide. In one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each RG′ is independently a divalent residue of RG where RG comprises an azide. In one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each RG′ is independently a divalent residue of RG where RG comprises an alkyne. In one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each RG′ is independently a divalent residue of RG where RG comprises a strained alkyne. In one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each RG′ is independently a divalent residue of RG where RG comprises an alkoxyamine. In one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each RG′ is independently -O-NH-. In one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each RG′ is independently . In one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each RG′ is independently a divalent residue of RG where each RG is independently selected from . one embodiment, provided is a conjugate of Formula (I′), (II′), (X′), or (XII′), wherein each RG′ is independently a divalent residue of RG where each RG is (XII′), wherein each RG′ is independently a divalent residue of RG where each RG is (XII′), wherein each RG′ is independently a divalent residue of RG where each RG is one embodiment, provided is a conjugate of Formula (I′) , wherein each RG′ is independently a divalent residue of RG where each [00132] In the conjugates described herein, each POLY can be any water-soluble polymer deemed useful by the person of skill in the art. Useful polymers are described here, and in the sections below. In certain embodiments, provided is a conjugate of Formula (I′)- (V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY is independently selected from polyethylene glycol (PEG), polyvinylpyrrolidone, polyglycerol, poly(N-2-hydroxypropyl) methacrylamide, and polyoxazoline. In one embodiment, provided is a conjugate of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY is polyethylene glycol (PEG). In one embodiment, provided is a conjugate of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY is polyvinylpyrrolidone. In one embodiment, provided is a conjugate of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY is polyglycerol. In one embodiment, provided is a conjugate of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY is poly(N-2-hydroxypropyl) methacrylamide. In one embodiment, provided is a conjugate of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY is polyoxazoline. In certain embodiments, provided is a conjugate of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY has a molecular weight independently selected from 5 kDa to 50 kDa. In certain embodiments, provided is a conjugate of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY has a molecular weight independently selected from 10 kDa to 25 kDa. In certain embodiments, provided is a conjugate of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY has a molecular weight of about 20 kDa. In certain embodiments, provided is a conjugate of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY is PEG having a molecular weight independently selected from 5 kDa to 50 kDa. In certain embodiments, provided is a conjugate of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY is PEG having a molecular weight independently selected from 10 kDa to 25 kDa. In certain embodiments, provided is a conjugate of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), or (XV′), wherein each POLY is PEG having a molecular weight of about 20 kDa. In certain embodiments, each POLY is uncapped (i.e., terminates with a hydroxyl). In certain embodiments, each POLY is methoxy-PEG (i.e., terminates with a methoxy). In certain embodiments, each PEG is linear. In certain embodiments, each PEG is branched. [00133] Provided are conjugates of the following formulae ,

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers, regioisomer, and/or mixture of regioisomers thereof. PRO, POLY, R 1 , R 4 , p, and w are as defined herein. [00134] In the formulae above, each R 1 is independently hydrogen, an electron donating group, or an electron withdrawing group. In one embodiment, each R 1 is hydrogen. In one embodiment, each R 1 is an electron donating group. In one embodiment, each R 1 is an electron withdrawing group. The electron donating group can be any electron donating group deemed suitable to the person of skill in the art. The electron withdrawing group can be any electron withdrawing group deemed suitable to the person of skill in the art. In certain embodiments, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein each R 1 is independently selected from the group consisting of hydrogen, haloalkyl, halogen, -CN, -SO 3 H, -C(O)R 3 , -C(O)OR 3 , -OR 3 , -N(H)C(O)R 3 , -N(H)CO 2 R 3 , and -N(H)C(O)C(H)(R 3 )CO2H wherein each R 3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. In certain embodiments, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein each R 1 is independently selected from the group consisting of hydrogen, -CF 3 , -Br, -Cl, -F, -CN, - SO3H, -C(O)Me, -CO2Me, -OMe, -N(H)C(O)Me, -N(H)CO2Me, and - N(H)C(O)C(H)(Me)CO 2 H. In certain embodiments, provided is a compound of Formula (I′)- (V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein each R 1 is independently selected from the group consisting of haloalkyl, halogen, -CN, -SO 3 H, -C(O)R 3 , -C(O)OR 3 , -OR 3 , -N(H)C(O)R 3 , -N(H)CO2R 3 , and -N(H)C(O)C(H)(R 3 )CO2H wherein each R 3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. In certain embodiments, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein each R 1 is independently selected from the group consisting of -CF3, -Br, -Cl, -F, -CN, -SO3H, -C(O)Me, -CO2Me, -OMe, -N(H)C(O)Me, - N(H)CO 2 Me, and -N(H)C(O)C(H)(Me)CO 2 H. In certain embodiments, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein each R 1 is independently selected from the group consisting of -CF 3 , -Br, -Cl, -F, - CN, -SO3H, -C(O)Me, -CO2Me, -OMe, -N(H)C(O)Me, -N(H)CO2Me, and -N(H)C(O)C(H)(Me)CO 2 H. In one embodiment, provided is a compound of Formula (I′)- (V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein R 1 is -Br. In one embodiment, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein R 1 is -Cl. In one embodiment, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein R 1 is - F. In one embodiment, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein R 1 is -CN. In one embodiment, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein R 1 is -SO 3 H. In one embodiment, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein R 1 is -C(O)Me. In one embodiment, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein R 1 is -OMe. [00135] In the formulae above, each R 4 is independently hydrogen or an electron withdrawing group. In one embodiment, each R 4 is hydrogen. In one embodiment, each R 4 is an electron withdrawing group. The electron withdrawing group can be any electron withdrawing group deemed suitable to the person of skill in the art. In certain embodiments, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein each R 4 is independently selected from the group consisting of -C(O)R 3 , - C(O)OR 3 , and -S(O)2R 3 , wherein each R 3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. In certain embodiments, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein each R 4 is independently selected from the group consisting of hydrogen, haloalkyl, - C(O)R 3 , -C(O)OR 3 , and -S(O) 2 CH 3 wherein each R 3 is independently alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl. In certain embodiments, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein each R 4 is independently selected from the group consisting of hydrogen, -CF3, - C(O)Me, -CO 2 Me, and -S(O) 2 CH 3 . In certain embodiments, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein each R 4 is independently selected from the group consisting of -C(O)Me, and -S(O) 2 R 3 . In one embodiment, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein R 4 is -C(O)Me. In one embodiment, provided is a compound of Formula (I′)-(V′), (X′), (XII′), (XIII′), (XIV′), (XV′), or compounds 101′-106′, wherein R 4 is -S(O)2CH3. Macromolecules (PRO) [00136] The macromolecule (PRO) can be any macromolecule deemed suitable by the person of skill in the art. In certain embodiments, the macromolecule is a protein, peptide, antibody or antigen binding fragment thereof, nucleic acid, carbohydrate, or other large molecule composed of polymerized monomers. In certain embodiments, the macromolecule is a protein. In certain embodiments, the macromolecule is an antibody, or an antigen binding fragment thereof. [00137] In certain embodiments, the macromolecule is selected from the group consisting of bone morphogenic protein, erythropoietin, G-CSF, GM-CSF, interferon alpha, interferon beta, interferon gamma, IL-2, and IL-11. In certain embodiments, the macromolecule is a cytokine. In certain embodiments, the macromolecule is an interleukin. In certain embodiments, the macromolecule is IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL- 9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL-27, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33, IL-34, IL-35, or IL-36. In one embodiment, the macromolecule is IL-2. In one embodiment, the macromolecule is an interferon. In one embodiment, the macromolecule is interferon alpha. In one embodiment, the macromolecule is interferon beta. In one embodiment, the macromolecule is interferon gamma. In one embodiment, the macromolecule is a tumor necrosis factor. In one embodiment, the macromolecule is TNF alpha. In one embodiment, the macromolecule is TNF beta. In one embodiment, the macromolecule is a transforming growth factor. In one embodiment, the macromolecule is a chemokine. In one embodiment, the macromolecule is G-CSF. In one embodiment, the macromolecule is GM-CSF. In one embodiment, the macromolecule is erythropoietin. In one embodiment, the macromolecule is alpha- galactosidase A. In one embodiment, the macromolecule is tissue plasminogen activator. In one embodiment, the macromolecule is insulin. In one embodiment, the macromolecule is insulin-like growth factor. [00138] In one embodiment, the macromolecule is an antibody or an antigen binding fragment thereof. Useful antibodies include, but are not limited to, rituximab (Rituxan®, IDEC/Genentech/Roche) (see, e.g., U.S. Pat. No. 5,736,137), a chimeric anti-CD20 antibody approved to treat Non-Hodgkin's lymphoma; HuMax-CD20, an anti-CD20 currently being developed by Genmab, an anti-CD20 antibody described in U.S. Pat. No. 5,500,362, AME- 133 (Applied Molecular Evolution), hA20 (Immunomedics, Inc.), HumaLYM (Intracel), and PRO70769 (PCT Application No. PCT/US2003/040426), trastuzumab (Herceptin®, Genentech) (see, e.g., U.S. Pat. No.5,677,171), a humanized anti-Her2/neu antibody approved to treat breast cancer; pertuzumab (rhuMab-2C4, Omnitarg®), currently being developed by Genentech; an anti-Her2 antibody (U.S. Pat. No. 4,753,894; cetuximab (Erbitux®, Imclone) (U.S. Pat. No.4,943,533; PCT Publication No. WO 96/40210), a chimeric anti-EGFR antibody in clinical trials for a variety of cancers; ABX-EGF (U.S. Pat. No.6,235,883), currently being developed by Abgenix-Immunex-Amgen; HuMax-EGFr (U.S. Pat. No. 7,247,301), currently being developed by Genmab; 425, EMD55900, EMD62000, and EMD72000 (Merck KGaA) (U.S. Pat. No. 5,558,864; Murthy, et al. (1987) Arch. Biochem. Biophys. 252(2): 549-60; Rodeck, et al. (1987) J. Cell. Biochem. 35(4): 315-20; Kettleborough, et al. (1991) Protein Eng.4(7): 773-83); ICR62 (Institute of Cancer Research) (PCT Publication No. WO 95/20045; Modjtahedi, et al. (1993) J. Cell. Biophys. 22(I-3): 129-46; Modjtahedi, et al. (1993) Br. J. Cancer 67(2): 247-53; Modjtahedi, et al. (1996) Br. J. Cancer 73(2): 228-35; Modjtahedi, et al. (2003) Int. J. Cancer 105(2): 273-80); TheraCIM hR3 (YM Biosciences, Canada and Centro de Immunologia Molecular, Cuba (U.S. Pat. No. 5,891,996; U.S. Pat. No. 6,506,883; Mateo, et al. (1997) Immunotechnol. 3(1): 71-81); mAb-806 (Ludwig Institute for Cancer Research, Memorial Sloan-Kettering) (Jungbluth, et al. (2003) Proc. Natl. Acad. Sci. USA.100(2): 639- 44); KSB-102 (KS Biomedix); MR1-1 (IVAX, National Cancer Institute) (PCT Publication No. WO 01/62931A2); and SC100 (Scancell) (PCT Publication No. WO 01/88138); alemtuzumab (Campath®, Millenium), a humanized mAb currently approved for treatment of B-cell chronic lymphocytic leukemia; muromonab-CD3 (Orthoclone OKT3®), an anti-CD3 antibody developed by Ortho Biotech/Johnson & Johnson, ibritumomab tiuxetan (Zevalin®), an anti-CD20 antibody developed by IDEC/Schering AG, gemtuzumab ozogamicin (Mylotarg®), an anti-CD33 (p67 protein) antibody developed by Celltech/Wyeth, alefacept (Amevive®), an anti-LFA-3 Fc fusion developed by Biogen), abciximab (ReoPro®), developed by Centocor/Lilly, basiliximab (Simulect®), developed by Novartis, palivizumab (Synagis®), developed by Medimmune, infliximab (Remicade®), an anti-TNFalpha antibody developed by Centocor, adalimumab (Humira®), an anti-TNFalpha antibody developed by Abbott, Humicade®, an anti-TNFalpha antibody developed by Celltech, golimumab (CNTO- 148), a fully human TNF antibody developed by Centocor, etanercept (Enbrel®), an p75 TNF receptor Fc fusion developed by Immunex/Amgen, Ienercept, an p55TNF receptor Fc fusion previously developed by Roche, ABX-CBL, an anti-CD147 antibody being developed by Abgenix, ABX-IL8, an anti-IL8 antibody being developed by Abgenix, ABX-MA1, an anti- MUC18 antibody being developed by Abgenix, Pemtumomab (R1549, 90Y-muHMFG1), an anti-MUC1 in development by Antisoma, Therex (R1550), an anti-MUC1 antibody being developed by Antisoma, AngioMab (AS1405), being developed by Antisoma, HuBC-1, being developed by Antisoma, Thioplatin (AS1407) being developed by Antisoma, Antegren® (natalizumab), an anti-alpha-4-beta-1 (VLA-4) and alpha-4-beta-7 antibody being developed by Biogen, VLA-1 mAb, an anti-VLA-1 integrin antibody being developed by Biogen, LTBR mAb, an anti-lymphotoxin beta receptor (LTBR) antibody being developed by Biogen, CAT- 152, an anti-TGF-β antibody being developed by Cambridge Antibody Technology, ABT 874 (J695), an anti-IL-12 p40 antibody being developed by Abbott, CAT-192, an anti-TGFβ1 antibody being developed by Cambridge Antibody Technology and Genzyme, CAT-213, an anti-Eotaxin1 antibody being developed by Cambridge Antibody Technology, LymphoStat- B® an anti-Blys antibody being developed by Cambridge Antibody Technology and Human Genome Sciences Inc., TRAIL-R1 mAb, an anti-TRAIL-R1 antibody being developed by Cambridge Antibody Technology and Human Genome Sciences, Inc., Avastin® bevacizumab, rhuMAb-VEGF), an anti-VEGF antibody being developed by Genentech, an anti-HER receptor family antibody being developed by Genentech, Anti-Tissue Factor (ATF), an anti- Tissue Factor antibody being developed by Genentech, Xolair® (Omalizumab), an anti-IgE antibody being developed by Genentech, Raptiva® (Efalizumab), an anti-CD11a antibody being developed by Genentech and Xoma, MLN-02 Antibody (formerly LDP-02), being developed by Genentech and Millenium Pharmaceuticals, HuMax CD4, an anti-CD4 antibody being developed by Genmab, HuMax-IL15, an anti-IL15 antibody being developed by Genmab and Amgen, HuMax-Inflam, being developed by Genmab and Medarex, HuMax- Cancer, an anti-Heparanase I antibody being developed by Genmab and Medarex and Oxford GlycoSciences, HuMax-Lymphoma, being developed by Genmab and Amgen, HuMax-TAC, being developed by Genmab, IDEC-131, and anti-CD40L antibody being developed by IDEC Pharmaceuticals, IDEC-151 (Clenoliximab), an anti-CD4 antibody being developed by IDEC Pharmaceuticals, IDEC-114, an anti-CD80 antibody being developed by IDEC Pharmaceuticals, IDEC-152, an anti-CD 23 being developed by IDEC Pharmaceuticals, anti- macrophage migration factor (MIF) antibodies being developed by IDEC Pharmaceuticals, BEC2, an anti-idiotypic antibody being developed by Imclone, IMC-1C11, an anti-KDR antibody being developed by Imclone, DC101, an anti-flk-1 antibody being developed by Imclone, anti-VE cadherin antibodies being developed by Imclone, CEA-Cide® (Iabetuzumab), an anti-carcinoembryonic antigen (CEA) antibody being developed by Immunomedics, LymphoCide® (Epratuzumab), an anti-CD22 antibody being developed by Immunomedics, AFP-Cide, being developed by Immunomedics, MyelomaCide, being developed by Immunomedics, LkoCide, being developed by Immunomedics, ProstaCide, being developed by Immunomedics, MDX-010, an anti-CTLA4 antibody being developed by Medarex, MDX-060, an anti-CD30 antibody being developed by Medarex, MDX-070 being developed by Medarex, MDX-018 being developed by Medarex, Osidem® (IDM-1), and anti- Her2 antibody being developed by Medarex and Immuno-Designed Molecules, HuMax®- CD4, an anti-CD4 antibody being developed by Medarex and Genmab, HuMax-IL15, an anti- IL15 antibody being developed by Medarex and Genmab, CNTO 148, an anti-TNFα antibody being developed by Medarex and Centocor/J&J, CNTO 1275, an anti-cytokine antibody being developed by Centocor/J&J, MOR101 and MOR102, anti-intercellular adhesion molecule-1 (ICAM-1) (CD54) antibodies being developed by MorphoSys, MOR201, an anti-fibroblast growth factor receptor 3 (FGFR-3) antibody being developed by MorphoSys, Nuvion® (visilizumab), an anti-CD3 antibody being developed by Protein Design Labs, HuZAF®, an anti-gamma interferon antibody being developed by Protein Design Labs, Anti-α5β1 Integrin, being developed by Protein Design Labs, anti-IL-12, being developed by Protein Design Labs, ING-1, an anti-Ep-CAM antibody being developed by Xoma, Xolair® (Omalizumab) a humanized anti-IgE antibody developed by Genentech and Novartis, and MLN01, an anti- Beta2 integrin antibody being developed by Xoma. [00139] In another embodiment, the therapeutics include KRN330 (Kirin); huA33 antibody (A33, Ludwig Institute for Cancer Research); CNTO 95 (alpha V integrins, Centocor); MEDI-522 (alpha Vβ3integrin, Medimmune); volociximab (alpha Vβ1 integrin, Biogen/PDL); Human mAb 216 (B cell glycosolated epitope, NCl); BiTE MT103 (bispecific CD19×CD3, Medimmune); 4G7×H22 (Bispecific Bcell×FcgammaR1, Medarex/Merck KGa); rM28 (Bispecific CD28×MAPG, EP Patent No. EP1444268); MDX447 (EMD 82633) (Bispecific CD64×EGFR, Medarex); Catumaxomab (removab) (Bispecific EpCAM× anti- CD3, Trion/Fres); Ertumaxomab (bispecific HER2/CD3, Fresenius Biotech); oregovomab (OvaRex) (CA-125, ViRexx); Rencarex® (WX G250) (carbonic anhydrase IX, Wilex); CNTO 888 (CCL2, Centocor); TRC105 (CD105 (endoglin), Tracon); BMS-663513 (CD137 agonist, Bristol Myers Squibb); MDX-1342 (CD19, Medarex); Siplizumab (MEDI-507) (CD2, Medimmune); Ofatumumab (Humax-CD20) (CD20, Genmab); Rituximab (Rituxan) (CD20, Genentech); veltuzumab (hA20) (CD20, Immunomedics); Epratuzumab (CD22, Amgen); lumiliximab (IDEC 152) (CD23, Biogen); muromonab-CD3 (CD3, Ortho); HuM291 (CD3 fc receptor, PDL Biopharma); HeFi-1, CD30, NCl); MDX-060 (CD30, Medarex); MDX-1401 (CD30, Medarex); SGN-30 (CD30, Seattle Genentics); SGN-33 (Lintuzumab) (CD33, Seattle Genentics); Zanolimumab (HuMax-CD4) (CD4, Genmab); HCD122 (CD40, Novartis); SGN- 40 (CD40, Seattle Genentics); MabCampath (Alemtuzumab) (CD52, Genzyme); MDX-1411 (CD70, Medarex); hLL1 (EPB-1) (CD74.38, Immunomedics); Galiximab (IDEC-144) (CD80, Biogen); MT293 (TRC093/D93) (cleaved collagen, Tracon); HuLuc63 (CS1, PDL Pharma); ipilimumab (MDX-010) (CTLA4, Bristol Myers Squibb); Tremelimumab (Ticilimumab, CP- 675,2) (CTLA4, Pfizer); HGS-ETR1 (Mapatumumab) (DR4TRAIL-R1 agonist, Human Genome Science/Glaxo Smith Kline); AMG-655 (DR5, Amgen); Apomab (DR5, Genentech); CS-1008 (DR5, Daiichi Sankyo); HGS-ETR2 (lexatumumab) (DR5TRAIL-R2 agonist, HGS); Cetuximab (Erbitux) (EGFR, Imclone); IMC-11F8, (EGFR, Imclone); Nimotuzumab (EGFR, YM Bio); Panitumumab (Vectabix) (EGFR, Amgen); Zalutumumab (HuMaxEGFr) (EGFR, Genmab); CDX-110 (EGFRvIII, AVANT Immunotherapeutics); adecatumumab (MT201) (Epcam, Merck); edrecolomab (Panorex, 17-1A) (Epcam, Glaxo/Centocor); MORAb-003 (folate receptor a, Morphotech); KW-2871 (ganglioside GD3, Kyowa); MORAb-009 (GP-9, Morphotech); CDX-1307 (MDX-1307) (hCGb, Celldex); Trastuzumab (Herceptin) (HER2, Celldex); Pertuzumab (rhuMAb 2C4) (HER2 (DI), Genentech); apolizumab (HLA-DR beta chain, PDL Pharma); AMG-479 (IGF-1R, Amgen); anti-IGF-1R R1507 (IGF1-R, Roche); CP 751871 (IGF1-R, Pfizer); IMC-A12 (IGF1-R, Imclone); BIIB022 (IGF-1R, Biogen); Mik- beta-1 (IL-2Rb (CD122), Hoffman-La Roche); CNTO 328 (IL6, Centocor); Anti-KIR (1-7F9) (Killer cell Ig-like Receptor (KIR), Novo); Hu3S193 (Lewis (y), Wyeth, Ludwig Institute of Cancer Research); hCBE-11 (LTβR, Biogen); HuHMFG1 (MUC1, Antisoma/NCl); RAV12 (N-linked carbohydrate epitope, Raven); CAL (parathyroid hormone-related protein (PTH-rP), University of California); CT-011 (PD1, CureTech); MDX-1106 (ono-4538) (PD1, Medarex/Ono); MAb CT-011 (PD1, Curetech); IMC-3G3 (PDGFRa, Imclone); bavituximab (phosphatidylserine, Peregrine); huJ591 (PSMA, Cornell Research Foundation); muJ591 (PSMA, Cornell Research Foundation); GC1008 (TGFb (pan) inhibitor (IgG4), Genzyme); Infliximab (Remicade) (TNFa, Centocor); A27.15 (transferrin receptor, Salk Institute, INSERN WO 2005/111082); E2.3 (transferrin receptor, Salk Institute); Bevacizumab (Avastin) (VEGF, Genentech); HuMV833 (VEGF, Tsukuba Research Lab, PCT Publication No. WO/2000/034337, University of Texas); IMC-18F1 (VEGFR1, Imclone); IMC-1121 (VEGFR2, Imclone). [00140] Examples of useful bispecific antibodies include, but are not limited to, those with one antibody directed against a tumor cell antigen and the other antibody directed against a cytotoxic trigger molecule such as anti-FcγRI/anti-CD 15, anti-p185 HER2 /FcγRIII (CD16), anti-CD3/anti-malignant B-cell (1D10), anti-CD3/anti-p185 HER2 , anti-CD3/anti-p97, anti- CD3/anti-renal cell carcinoma, anti-CD3/anti-OVCAR-3, anti-CD3/L-D1 (anti-colon carcinoma), anti-CD3/anti-melanocyte stimulating hormone analog, anti-EGF receptor/anti- CD3, anti-CD3/anti-CAMA1, anti-CD3/anti-CD19, anti-CD3/MoV18, anti-neural cell adhesion molecule (NCAM)/anti-CD3, anti-folate binding protein (FBP)/anti-CD3, anti-pan carcinoma associated antigen (AMOC-31)/anti-CD3; bispecific antibodies with one antibody which binds specifically to a tumor antigen and another antibody which binds to a toxin such as anti-saporin/anti-Id-1, anti-CD22/anti-saporin, anti-CD7/anti-saporin, anti-CD38/anti- saporin, anti-CEA/anti-ricin A chain, anti-interferon-α (IFN-α)/anti-hybridoma idiotype, anti- CEA/anti-vinca alkaloid; bispecific antibodies for converting enzyme activated prodrugs such as anti-CD30/anti-alkaline phosphatase (which catalyzes conversion of mitomycin phosphate prodrug to mitomycin alcohol); bispecific antibodies which can be used as fibrinolytic agents such as anti-fibrin/anti-tissue plasminogen activator (tPA), anti-fibrin/anti-urokinase-type plasminogen activator (uPA); bispecific antibodies for targeting immune complexes to cell surface receptors such as anti-low density lipoprotein (LDL)/anti-Fc receptor (e.g., FcγRI, FcγRII or FcγRIII); bispecific antibodies for use in therapy of infectious diseases such as anti- CD3/anti-herpes simplex virus (HSV), anti-T-cell receptor:CD3 complex/anti-influenza, anti- FcγR/anti-HIV; bispecific antibodies for tumor detection in vitro or in vivo such as anti- CEA/anti-EOTUBE, anti-CEA/anti-DPTA, anti- anti-p185 HER2 /anti-hapten; bispecific antibodies as vaccine adjuvants (see Fanger, M W et al., Crit Rev Immunol.1992; 12(34):101- 24, which is incorporated by reference herein); and bispecific antibodies as diagnostic tools such as anti-rabbit IgG/anti-ferritin, anti-horse radish peroxidase (HRP)/anti-hormone, anti- somatostatin/anti-substance P, anti-HRP/anti-FITC, anti-CEA/anti-β-galactosidase (see Nolan, O. and O'Kennedy, R., Biochim Biophys Acta. 1990 Aug. 1; 1040(1):1-11, which is incorporated by reference herein). Examples of trispecific antibodies include anti-CD3/anti- CD4/anti-CD37, anti-CD3/anti-CD5/anti-CD37 and anti-CD3/anti-CD8/anti-CD37. Conjugation [00141] In certain embodiments, the conjugate can be formed from a macromolecule that comprises one or more reactive groups. In certain embodiments, the conjugate can be formed from a macromolecule comprising all naturally encoded amino acids. Those of skill in the art will recognize that several naturally encoded amino acids include reactive groups capable of conjugation to a fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound or to a linker. These reactive groups include cysteine side chains, lysine side chains, and amino-terminal groups. In these embodiments, the conjugate can comprise a fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound or linker linked to the residue of an antibody reactive group. In these embodiments, the fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound precursor or linker precursor comprises a reactive group capable of forming a bond with an antibody or antigen binding fragment thereof reactive group. Typical reactive groups include maleimide groups, activated carbonates (including, but not limited to, p-nitrophenyl ester), activated esters (including, but not limited to, N-hydroxysuccinimide, p-nitrophenyl ester, and aldehydes). Particularly useful reactive groups include maleimide and succinimide, for instance N- hydroxysuccinimide, for forming bonds to cysteine and lysine side chains. Further reactive groups are described in the sections and examples below. [00142] In further embodiments, the macromolecule comprises one or more modified amino acids having a reactive group, as described herein. Typically, the modified amino acid is not a naturally encoded amino acid. These modified amino acids can comprise a reactive group useful for forming a covalent bond to a linker precursor or to a fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound precursor. One of skill in the art can use the reactive group to link the macromolecule to any molecular entity capable of forming a covalent bond to the modified amino acid. Thus, provided herein are conjugates comprising a macromolecule comprising a modified amino acid residue linked to a macromolecule directly or indirectly via a linker. Exemplary modified amino acids are described in the sections below. Generally, the modified amino acids have reactive groups capable of forming bonds to linkers or fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compounds with complementary reactive groups. [00143] In certain embodiments, the non-natural amino acids are positioned at select locations in a polypeptide chain of the macromolecule. These locations were identified as providing optimum sites for substitution with the non-natural amino acids. Each site is capable of bearing a non-natural amino acid with optimum structure, function, and/or methods for producing the macromolecule. [00144] In certain embodiments, a site-specific position for substitution provides a macromolecule that is stable. Stability can be measured by any technique apparent to those of skill in the art. In certain embodiments, a site-specific position for substitution provides a macromolecule that has optimal functional properties. [00145] In certain embodiments, the macromolecules comprise one or more non-natural amino acids suitable for conjugation. In certain embodiments, the macromolecules provided herein comprise one, or more than one, non-natural amino acids at site-specific positions. For example, in one embodiment, at least one of the non-natural amino acid residues is a pAMF residue. In certain embodiments, the macromolecules provided herein comprise two non- natural amino acids at site-specific positions. For example, in one embodiment, the macromolecule, such as an antibody or an antigen binding fragment thereof, includes a Y180 pAMF mutation, a F404 pAMF mutation, or both. In certain embodiments, the macromolecules provided herein comprise three non-natural amino acids at site-specific positions. In certain embodiments, the macromolecules provided herein comprise more than three non-natural amino acids at site-specific positions. [00146] In certain embodiments, the macromolecules provided herein are antibodies or antigen binding fragments thereof comprising one or more non-natural amino acids each at a position independently selected from the group consisting of heavy chain or light chain residues HC-F404, HC-K121, HC-Y180, HC-F241, HC-221, LC-T22, LC-S7, LC-N152, LC- K42, LC-E161, LC-D170, HC-S136, HC-S25, HC-A40, HC-S119, HC-S190, HC-K222, HC- R19, HC-Y52, or HC-S70, according to the Kabat, Chothia, or EU numbering scheme, or a post-translationally modified variant thereof. In certain embodiments, the antibodies provided herein comprise one or more non-natural amino acids each at a position independently selected from the group consisting of HC-180, HC-222, LC-7, and LC-42, according to the Kabat, Chothia, or EU numbering scheme, or a post-translationally modified variant thereof. In these designations, HC indicates a heavy chain residue, and LC indicates a light chain residue. In certain embodiments, the non-natural amino acids are at HC-F404. In certain embodiments, the non-natural amino acids are at HC-Y180. In certain embodiments, the non-natural amino acids are at HC-F404 and HC-Y180. In certain embodiments, the non-natural amino acids are at HC-K222. In certain embodiments, the non-natural amino acids are at LC-S7. In certain embodiments, the non-natural amino acids are at LC-K42. In certain embodiments, the non- natural amino acids are at HC-Y180, HC-K222, LC-S7, and LC-K42. In certain embodiments, the non-natural amino acids are the same. In certain embodiments, the non-natural amino acids are different. In certain embodiments, the non-natural amino acids are residues of Formula (30), herein. [00147] In some embodiments, the macromolecule sequence may encompass a Q-tag sequence that is compatible with transglutaminase conjugation. In some embodiments, the one or more glutamine residues are in Q-tags independently selected from the group consisting of LLQGG, YAHQAHY, YRYRQ, PNPQLPF, PKPQQFM, GQQQLG, WALQRPH, WELQRPY, YPMQGWF, LSLSQG, GGGLLQGG, GLLQG, GSPLAQSHGG, GLLQGGG, GLLQGG, GLLQ, LLQLLQGA, LLQGA, LLQYQGA, LLQGSG, LLQYQG, LLQLLQG, SLLQG, LLQLQ, LLQLLQ, LLQGR, LLQGPA, LLQGPP, or GGLLQGPP. [00148] In some embodiments, the acyl donor glutamine-containing tag comprises at least one glutamine (Gln, or Q). In some embodiments, the acyl donor glutamine-containing tag comprises an amino acid sequence XXQX, wherein X is any amino acid (e.g., conventional amino acid Leu, Ala, Gly, Ser, Val, Phe, Tyr, His, Arg, Asn, Glu, Asp, Cys, Gln, Ile, Met, Pro, Thr, Lys, or Trp, or nonconventional amino acid). In some embodiments, the acyl donor glutamine-containing tag (Q-tag) comprises an amino acid sequence selected from the group consisting of LLQGG, LLQG, LSLSQG, GGGLLQGG, GLLQG, GSPLAQSHGG, GLLQGGG, GLLQGG, GLLQ, LLQLLQGA, LLQGA, LLQYQGA, LLQGSG, LLQYQG, LLQLLQG, SLLQG, LLQLQ, LLQLLQ, and LLQGR. In some embodiments, the acyl donor glutamine-containing tag (Q-tag) comprises an amino acid sequence selected from the group consisting of LLQGPA, LLQGPP, and GGLLQGPP. In some embodiments, the acyl donor glutamine-containing tag (Q-tag) comprises an amino acid sequence selected from the group consisting of LLQGG and LLQGA. In such embodiments, a linker-fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound bearing an amino group can be conjugated to the side chain of one or more glutamine (Q) residues in the macromolecule in the presence of transglutaminase. Reactive Groups [00149] Reactive groups facilitate conjugation of the fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compounds described herein to a second compound, such as an macromolecule described herein. In certain embodiments, the reactive group is designated RG herein. Reactive groups can react via any suitable reaction mechanism known to those of skill in the art. In certain embodiments, a reactive group reacts through a [3+2] alkyne-azide cycloaddition reaction, inverse-electron demand Diels-Alder ligation reaction, thiol- electrophile reaction, or carbonyl-oxyamine reaction, as described in detail herein. In certain embodiments, the reactive group comprises an alkyne, strained alkyne, tetrazine, thiol, para- acetyl-phenylalanine residue, oxyamine, maleimide, or azide. In certain embodiments, the reactive group is:

certain embodiments, R 201 is methyl, ethyl, or propyl. In one embodiment, R 201 is methyl. In one embodiment, R 201 is ethyl. In one embodiment, R 201 is propyl. Additional reactive groups are described in, for example, U.S. Patent Application Publication No. 2014/0356385, U.S. Patent Application Publication No. 2013/0189287, U.S. Patent Application Publication No.2013/0251783, U.S. Patent No. 8,703,936, U.S. Patent No. 9,145,361, U.S. Patent No.9,222,940, and U.S. Patent No.8,431,558. [00150] After conjugation, a divalent residue of the reactive group (viz., RG′) is formed and is bonded to the residue of a second compound. The structure of the divalent residue is determined by the type of conjugation reaction employed to form the conjugate. [00151] In certain embodiments when a conjugate is formed through a [3+2] alkyne- azide cycloaddition reaction, the divalent residue of the reactive group (e.g., RG′) comprises a triazole ring or fused cyclic group comprising a triazole ring. In certain embodiments, when a conjugate is formed through a strain-promoted [3+2] alkyne-azide cycloaddition (SPAAC) reaction, the divalent residue of the reactive group (e.g., RG′) is: In certain embodiments, when a conjugate is formed through a tetrazine inverse electron demand Diels-Alder ligation reaction, the divalent residue of the reactive group (e.g., RG′) comprises a fused bicyclic ring having at least two adjacent nitrogen atoms in the ring. In certain embodiments, when a conjugate is formed through a tetrazine inverse electron demand Diels-Alder ligation reaction, the divalent residue of the reactive group (e.g., RG′) is . In certain embodiments, when a conjugate is formed through a thiol-maleimide reaction, the divalent residue of the reactive group comprises sulfur linkage. In certain embodiments, when a conjugate is formed through a thiol-maleimide, , reaction the divalent residue of the reactive group certain embodiments when a conjugate is formed through an oxime conjugation reaction, the divalent residue of the reactive group comprises a divalent residue of a non-natural amino acid. In certain embodiments when a conjugate is formed through an oxime conjugation reaction, the divalent residue of the reactive group ( . In certain embodiments when a conjugate is formed through an oxime conjugation reaction, the divalent residue of the reactive group comprises an oxime linkage. In certain embodiments when a conjugate is formed through an oxime conjugation reaction, the divalent residue of the reactive group [00152] In particular embodiments, provided herein are conjugates wherein the macromolecule comprises a residue of a non-natural amino acid according to Formula (30), below. In particular embodiments, provided herein are conjugates wherein the macromolecule is an antibody or antigen binding fragment thereof comprising a residue of a non-natural amino acid according to Formula (30), below, at heavy chain position 404 according to the EU numbering system (30). [00153] Those of skill will recognize that amino acids such as Formula (30) are incorporated into macromolecules as residues. For instance, a residue of Formula (30) can be according to the following Formula (30′) Further modification, for instance at -N 3 is also contemplated and encompassed within the term “residue” herein. [00154] In particular embodiments, provided herein are conjugates wherein the macromolecule comprises a residue of a non-natural amino acid according to Formula (56), below. In particular embodiments, provided herein are conjugates wherein the macromolecule is an antibody or antigen binding fragment thereof comprising a residue of the non-natural amino acid according to Formula (56), below, at heavy chain position 404 according to the EU numbering system. The non-natural amino acid according to Formula (56) is [00155] In particular embodiments, provided herein are conjugates wherein the macromolecule comprises a non-natural amino acid residue of para-azidomethyl-L- phenylalanine. In particular embodiments, provided herein are conjugates wherein the macromolecule is an antibody or antigen binding fragment thereof comprising a residue of the non-natural amino acid residue para-azidomethyl-L-phenylalanine at heavy chain position 404 according to the EU numbering system [00156] In particular embodiments, provided herein are conjugates wherein the macromolecule comprises a non-natural amino acid residue of para-acetyl-L-phenylalanine. In particular embodiments, provided herein are conjugates wherein the macromolecule is an antibody or antigen binding fragment thereof comprising a residue of the non-natural amino acid residue para-acetyl-L-phenylalanine at heavy chain position 404 according to the EU numbering system.. Water soluble polymers [00157] In certain embodiments, the conjugate comprises one or more water soluble polymers. A wide variety of macromolecular polymers and other molecules can be linked to the polypeptides described herein to modulate biological properties of the polypeptide, and/or provide new biological properties to the polypeptide. These macromolecular polymers can be linked to the polypeptide via a naturally encoded amino acid, via a non-naturally encoded amino acid, or any functional substituent of a natural or modified amino acid, or any substituent or functional group added to a natural or modified amino acid. The molecular weight of the polymer may include a wide range including, but not limited to, between about 100 Da and about 100,000 Da or more. [00158] The polymer selected may be water soluble so that a protein to which it is attached does not precipitate in an aqueous environment, such as a physiological environment. The polymer may be branched or unbranched. In certain embodiments, for therapeutic use of the end-product preparation, the polymer will be pharmaceutically acceptable. [00159] In certain embodiments, the proportion of polyethylene glycol molecules to polypeptide molecules will vary, as will their concentrations in the reaction mixture. In general, the optimum ratio (in terms of efficiency of reaction in that there is minimal excess unreacted protein or polymer) may be determined by the molecular weight of the polyethylene glycol selected and on the number of available reactive groups available. Regarding molecular weight, typically the higher the molecular weight of the polymer, the fewer number of polymer molecules which may be attached to the protein. Similarly, branching of the polymer should be taken into account when optimizing these parameters. Generally, the higher the molecular weight (or the more branches) the higher the polymer:protein ratio. [00160] The water soluble polymer may be any structural form including, but not limited to, linear, forked, or branched. Typically, the water soluble polymer is a poly(alkylene glycol), such as poly(ethylene glycol) (PEG), but other water soluble polymers can also be employed. By way of example, PEG is used to describe certain embodiments. [00161] PEG is a well-known, water soluble polymer that is commercially available or can be prepared by ring-opening polymerization of ethylene oxide according to methods well known in the art (Sandler and Karo, Polymer Synthesis, Academic Press, New York, Vol. 3, pages 138-161). The term “PEG” is used broadly to encompass any polyethylene glycol molecule, without regard to size or to modification at an end of a PEG, and can be represented as linked to a polypeptide by the formula: X′O–(CH 2 CH 2 O) n –CH 2 CH 2 –Y where n is an integer selected from 2 to 10,000, X′ is hydrogen or a terminal modification including, but not limited to, C 1-4 alkyl, and Y is the attachment point to the polypeptide. [00162] In some cases, a PEG terminates on one end with hydroxy or methoxy, i.e., X′ is hydrogen or CH 3 (aka “methoxy PEG”). Alternatively, the PEG can terminate with a PEG reactive group, thereby forming a bifunctional polymer. Typical PEG reactive groups can include those reactive groups that are commonly used to react with the functional groups found in the twenty common amino acids (including, but not limited to, maleimide groups, activated carbonates (including, but not limited to, p-nitrophenyl ester), activated esters (including, but not limited to, N-hydroxysuccinimide, p-nitrophenyl ester, and aldehydes) as well as functional groups that are inert to the twenty common amino acids, but that react specifically with complementary functional groups present in non-naturally encoded amino acids (including, but not limited to, azide groups and/or alkyne groups). It is noted that the other end of the PEG, which is shown in the above formula by Y, will attach either directly or indirectly to a polypeptide via a naturally-occurring or non-naturally encoded amino acid. For instance, Y may be an amide, carbamate, or urea linkage to an amine group (including, but not limited to, the epsilon amine of lysine or the N-terminus) of the polypeptide. Alternatively, Y may be a maleimide linkage to a thiol group (including, but not limited to, the thiol group of cysteine). Alternatively, Y may be a linkage to a residue not commonly accessible via the twenty common amino acids. For example, an azide group on the PEG can be reacted with an alkyne group on the polypeptide to form a Huisgen [3+2] cycloaddition product. Alternatively, an alkyne group on the PEG can be reacted with an azide group present in a non-naturally encoded amino acid, such as the modified amino acids described herein, to form a similar product. In some embodiments, a strong nucleophile (including, but not limited to, hydrazine, hydrazide, hydroxylamine, or semicarbazide) can be reacted with an aldehyde or ketone group present in a non-naturally encoded amino acid to form a hydrazone, oxime, or semicarbazone, as applicable, which in some cases can be further reduced by treatment with an appropriate reducing agent. Alternatively, the strong nucleophile can be incorporated into the polypeptide via a non-naturally encoded amino acid and used to react preferentially with a ketone or aldehyde group present in the water soluble polymer. [00163] Any molecular mass for a PEG can be used as practically desired including, but not limited to, from about 100 Daltons (Da) to 100,000 Da or more as desired (including, but not limited to, in certain embodiments 0.1-50 kDa or 10-40 kDa). Branched chain PEGs including, but not limited to, PEG molecules with each chain having a molecular weight (MW) ranging from 1-100 kDa (including, but not limited to, 1-50 kDa or 5-20 kDa) can also be used. A wide range of PEG molecules are described in the Shearwater Polymers, Inc. catalog, and the Nektar Therapeutics catalog, each incorporated herein by reference. [00164] Generally, at least one terminus of the PEG molecule is available for reaction with the remainder of the fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound. For example, PEG derivatives bearing alkyne and azide moieties for reaction with amino acid side chains can be used to attach PEG to non-naturally encoded amino acids as described herein. If the non-naturally encoded amino acid comprises an azide, then the PEG will typically contain either an alkyne moiety to effect formation of the [3+2] cycloaddition product or an activated PEG species (i.e., ester, carbonate) containing a phosphine group to effect formation of the amide linkage. Alternatively, if the non-naturally encoded amino acid comprises an alkyne, then the PEG will typically contain an azide moiety to effect formation of the [3+2] Huisgen cycloaddition product. If the non-naturally encoded amino acid comprises a carbonyl group, the PEG will typically comprise a nucleophile (including, but not limited to, a hydrazide, hydrazine, hydroxylamine, or semicarbazide functionality) in order to effect formation of corresponding hydrazone, oxime, and semicarbazone linkages, respectively. In other alternatives, a reverse of the orientation of the reactive groups described herein can be used (i.e., an azide moiety in the non-naturally encoded amino acid can be reacted with a PEG derivative containing an alkyne). [00165] In some embodiments, the polypeptide variant with a PEG derivative contains a chemical functionality that is reactive with the chemical functionality present on the side chain of the non-naturally encoded amino acid. [00166] In certain embodiments, POLY is an azide- or acetylene-containing polymer comprising a water soluble polymer backbone having an average molecular weight from about 800 Da to about 100,000 Da. The polymer backbone of the water-soluble polymer can be poly(ethylene glycol). However, it should be understood that a wide variety of water soluble polymers including, but not limited to, poly(ethylene)glycol and other related polymers, including poly(dextran) and poly(propylene glycol), are also suitable for use and that the use of the term “PEG” or “poly(ethylene glycol)” is intended to encompass and include all such molecules. The term “PEG” further includes, but is not limited to, poly(ethylene glycol) in any of its forms, including bifunctional PEG, multiarmed PEG, derivatized PEG, forked PEG, branched PEG, pendent PEG (i.e., PEG or related polymers having one or more functional groups pendent to the polymer backbone), or PEG with degradable linkages therein. [00167] The polymer backbone can be linear or branched. Branched polymer backbones are generally known in the art. Typically, a branched polymer has a central branch core moiety and a plurality of linear polymer chains linked to the central branch core. PEG is commonly used in branched forms that can be prepared by addition of ethylene oxide to various polyols, such as glycerol, glycerol oligomers, pentaerythritol, and sorbitol. The central branch moiety can also be derived from several amino acids, such as lysine. The branched poly(ethylene glycol) can be represented in general form as R-(-PEG-OH) m in which R is derived from a core moiety, such as glycerol, glycerol oligomers, or pentaerythritol, and m represents the number of arms. Multi-armed PEG molecules, such as those described in U.S. Pat. Nos. 5,932,462; 5,643,575; 5,229,490; and 4,289,872; U.S. Pat. Appl. No. 2003/0143596; and WO 96/21469 and WO 93/21259, each of which is incorporated by reference herein in its entirety, can also be used as the polymer backbone. [00168] Branched PEG can also be in the form of a forked PEG represented by PEG(-YCHZ 2 ) n , where Y is a linking group and Z is an activated terminal group linked to CH by a chain of atoms of defined length. [00169] Yet another branched form, the pendant PEG, has PEG reactive groups, such as carboxyl, along the PEG backbone rather than at the end of PEG chains. [00170] In addition to these forms of PEG, the polymer can also be prepared with weak or degradable linkages in the backbone. For example, PEG can be prepared with ester linkages in the polymer backbone that are subject to hydrolysis. As shown herein, this hydrolysis results in cleavage of the polymer into fragments of lower molecular weight: -PEG-CO2-PEG- +H 2 O→PEG-CO 2 H+HO-PEG-. It is understood by those skilled in the art that the term “poly(ethylene glycol)” or “PEG” represents or includes all the forms known in the art including, but not limited to, those disclosed herein. [00171] Many other polymers are also suitable for use. In some embodiments, polymer backbones that are water-soluble, with from two to about three hundred termini, are particularly suitable. Examples of suitable polymers include, but are not limited to, other poly(alkylene glycols), such as poly(propylene glycol) (“PPG”), copolymers thereof (including, but not limited to, copolymers of ethylene glycol and propylene glycol), terpolymers thereof, mixtures thereof, and the like. Although the molecular weight of each chain of the polymer backbone can vary, it is typically in the range of from about 800 Da to about 100,000 Da, often from about 6,000 Da to about 80,000 Da. [00172] Those of ordinary skill in the art will recognize that the foregoing list for substantially water-soluble backbones is by no means exhaustive and is merely exemplary, and that all polymeric materials having the qualities described herein are contemplated as being suitable for use. [00173] In some embodiments the polymer derivatives are "multi-functional," meaning that the polymer backbone has at least two termini, and possibly as many as about 300 termini, functionalized or activated with a functional group. Multifunctional polymer derivatives include, but are not limited to, linear polymers having two termini, each terminus being bonded to a functional group which may be the same or different. Linkers [00174] In certain embodiments, the macromolecules can be linked to the fluorenylmethyloxycarbonyl and/or fluorenylmethylaminocarbonyl compounds with one or more linkers capable of reacting with a macromolecule amino acid and with a fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound. The one or more linkers can be any linkers apparent to those of skill in the art. [00175] The term “linker” is used herein to refer to groups or bonds that normally are formed as the result of a chemical reaction and typically are covalent linkages as defined above. [00176] Useful linkers include those described herein. In certain embodiments, the linker is any divalent or multivalent linker known to those of skill in the art. Useful divalent linkers include, carbonyl, alkylene, substituted alkylene, heteroalkylene, substituted heteroalkylene, arylene, substituted arylene, heteroarylene, and substituted heteroarylene. In certain embodiments, the linker is C1-10 alkylene or C1-10 heteroalkylene. In some embodiments, the C 1-10 heteroalkylene is PEG. [00177] In certain embodiments, the linker is hydrolytically stable. Hydrolytically stable linkers or linkages means that the linkers or linkages are substantially stable in water (i.e., do not react with water at useful pH values) including, but not limited to, physiological conditions for an extended period of time, perhaps even indefinitely in certain embodiments. In certain embodiments, the linker is hydrolytically unstable. Hydrolytically unstable or degradable linkers or linkages mean that the linkers or linkages are degradable in water or in aqueous solutions including, for example, blood. Enzymatically unstable or degradable linkers or linkages mean that the linkers or linkage can be degraded by one or more enzymes. [00178] As understood in the art, PEG and related polymers may include degradable linkages in the polymer backbone or in the linker group between the polymer backbone and one or more of the terminal functional groups of the polymer molecule. For example, ester linkages formed by the reaction of PEG carboxylic acids or activated PEG carboxylic acids with alcohol groups on a biologically active agent generally hydrolyze under physiological conditions to release the agent. [00179] Other hydrolytically degradable linkers or linkages include, but are not limited to, carbonate linkages; imine linkages resulting from reaction of an amine and an aldehyde or ketone; phosphate ester linkages formed by reacting an alcohol with a phosphate group; hydrazone linkages which are the reaction product of a hydrazide and an aldehyde or ketone; acetal linkages that are the reaction product of an aldehyde or ketone and an alcohol; orthoester linkages that are the reaction product of a nitrile and an alcohol; peptide linkages formed by an amine group including, but not limited to, at an end of a polymer such as PEG, and a carboxyl group of a peptide; and oligonucleotide linkages formed by a phosphoramidite groupat the end of a polymer, and a 5'-hydroxyl group of an oligonucleotide. [00180] A number of different cleavable linkers are known to those of skill in the art. See U.S. Pat. Nos. 4,618,492; 4,542,225; and 4,625,014. The mechanisms for release of an agent from these linker groups include, for example, irradiation of a photolabile bond and acid- catalyzed hydrolysis. U.S. Pat. No. 4,671,958, for example, includes a description of immunoconjugates comprising linkers that are cleaved at the target site in vivo by the proteolytic enzymes of the patient's complement system. The length of the linker may be predetermined or selected depending upon a desired spatial relationship between the polypeptide and the molecule linked to it. In view of the large number of methods that have been reported for attaching a variety of radiodiagnostic compounds, radiotherapeutic compounds, drugs, toxins, and other agents to polypeptides one skilled in the art will be able to determine a suitable method for attaching a given agent to a polypeptide. [00181] The linker may have a wide range of molecular weight or molecular length. Larger or smaller molecular weight linkers may be used to provide a desired spatial relationship or conformation between the polypeptide and the linked entity. Linkers having longer or shorter molecular length may also be used to provide a desired space or flexibility between the polypeptide and the linked entity. Similarly, a linker having a particular shape or conformation may be utilized to impart a particular shape or conformation to the polypeptide or the linked entity, either before or after the polypeptide reaches its target. The functional groups present on each end of the linker may be selected to modulate the release of a macromolecule under desired conditions. This optimization of the spatial relationship between the polypeptide and the linked entity may provide new, modulated, or desired properties to the molecule. [00182] In some embodiments, provided herein water-soluble bifunctional linkers that have a dumbbell structure that includes: a) an azide, an alkyne, a hydrazine, a hydrazide, a hydroxylamine, or a carbonyl-containing moiety on at least a first end of a polymer backbone; and b) at least a second functional group on a second end of the polymer backbone. The second functional group can be the same or different as the first functional group. The second functional group, in some embodiments, is not reactive with the first functional group. In some embodiments, water-soluble compounds that comprise at least one arm of a branched molecular structure are provided. For example, the branched molecular structure can be a dendritic structure. [00183] In some embodiments, the linker is derived from a linker precursor selected from the group consisting of N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), N-succinimidyl 4-(2-pyridyldithio)pentanoate (SPP), N-succinimidyl 4-(2- pyridyldithio)butanoate (SPDB), N-succinimidyl-4-(2-pyridyldithio)-2-sulfo-butanoate (sulfo-SPDB), N-succinimidyl iodoacetate (SIA), N-succinimidyl(4- iodoacetyl)aminobenzoate (SIAB), maleimide PEG NHS, N-succinimidyl 4-(maleimidomethyl)cyclohexanecarboxylate (SMCC), N-sulfosuccinimidyl 4-(maleimidomethyl)cyclohexanecarboxylate (sulfo-SMCC) or 2,5-dioxopyrrolidin-1-yl 17-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-5,8,11,14-tetraoxo -4,7,10,13-tetraazaheptadecan- 1-oate (CX1-1). In one embodiment, the linker is derived from the linker precursor N-succinimidyl 4-(maleimidomethyl)cyclohexanecarboxylate (SMCC). In one embodiment, the linker is derived from the linker precursor N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP). In one embodiment, the linker is derived from the linker precursor N-succinimidyl 4- (2-pyridyldithio)pentanoate (SPP). In one embodiment, the linker is derived from the linker precursor N-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB). In one embodiment, the linker is derived from the linker precursor N-succinimidyl-4-(2-pyridyldithio)-2-sulfo-butanoate (sulfo-SPDB). In one embodiment, the linker is derived from the linker precursor N- succinimidyl iodoacetate (SIA). In one embodiment, the linker is derived from the linker precursor N-succinimidyl(4-iodoacetyl)aminobenzoate (SIAB). In one embodiment, the linker is derived from the linker precursor maleimide PEG NHS. In one embodiment, the linker is derived from the linker precursor N-sulfosuccinimidyl 4-(maleimidomethyl)cyclohexanecarboxylate (sulfo-SMCC). In one embodiment, the linker is derived from the linker precursor 2,5-dioxopyrrolidin-1-yl 17-(2,5-dioxo-2,5-dihydro-1H- pyrrol-1-yl)-5,8,11,14-tetraoxo-4,7,10,13-tetraazaheptadecan -1-oate (CX1-1). [00184] In some embodiments, the linker is derived from a linker precursor selected from the group consisting of dipeptides, tripeptides, tetrapeptides, and pentapeptides. In such embodiments, the linker can be cleaved by a protease. Exemplary dipeptides include, but are not limited to, valine-citrulline (VC or val-cit), alanine-phenylalanine (AF or ala-phe); phenylalanine-lysine (FK or phe-lys); phenylalanine-homolysine (phe-homolys); and N-methyl-valine-citrulline (Me-val-cit). Exemplary tripeptides include, but are not limited to, glycine-valine-citrulline (gly-val-cit), glycine-glycine-glycine (gly-gly-gly), glycine- (methoxyethoxyethyl)serine-valine, and O-MeSerValAla). [00185] In some embodiments, a linker comprises a self-immolative spacer. In certain embodiments, the self-immolative spacer comprises p-aminobenzyl. In some embodiments, a p-aminobenzyl alcohol is attached to an amino acid unit via an amide bond, and a carbamate, methylcarbamate, or a carbonate is made between the benzyl alcohol and the payload (Hamann et al. (2005) Expert Opin. Ther. Patents (2005) 15:1087-1103). In some embodiments, the linker comprises p-aminobenzyloxycarbonyl (PABC). Other examples of self-immolative spacers include, but are not limited to, aromatic compounds that are electronically similar to the PABC group, such as 2-aminoimidazol-5-methanol derivatives (U.S. Pat. No. 7,375,078; Hay et al. (1999) Bioorg. Med. Chem. Lett. 9:2237) and ortho- or para-aminobenzylacetals. In some embodiments, spacers can be used that undergo cyclization upon amide bond hydrolysis, such as substituted and unsubstituted 4-aminobutyric acid amides (Rodrigues et al. (1995) Chemistry Biology 2:223), appropriately substituted bicyclo[2.2.1] and bicyclo[2.2.2] ring systems (Storm et al. (1972) J. Amer. Chem. Soc. 94:5815) and 2-aminophenylpropionic acid amides (Amsberry, et al. (1990) J. Org. Chem.55:5867). Linkage of a drug to the α-carbon of a glycine residue is another example of a self-immolative spacer that may be useful in conjugates (Kingsbury et al. (1984) J. Med. Chem.27:1447). [00186] In certain embodiments, linker precursors can be combined to form larger linkers. For instance, in certain embodiments, linkers comprise the dipeptide valine-citrulline and p-aminobenzyloxycarbonyl. These are also referenced as ValCit-PABC- linkers. [00187] In certain embodiments, the fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compounds can be linked to the linkers, referred to herein as a linker-fluorenylmethoxycarbonyl and/or linker-fluorenylmethylaminocarbonyl compounds, with one or more linker groups capable of reacting with an macromolecule amino acid group. The one or more linkers can be any linkers apparent to those of skill in the art or those set forth herein. [00188] Linker precursors can be prepared as described herein in the Examples section, and/or by standard techniques (e.g., WO 2019/055931, WO 2019/055909, WO 2017/132617, WO 2017/132615, each incorporated by reference in their entirety), or obtained from commercial sources. Compositions and Uses Pharmaceutical Compositions and Methods of Administration [00189] The conjugates provided herein can be formulated into pharmaceutical compositions using methods available in the art and those disclosed herein. Any of the conjugates provided herein can be provided in the appropriate pharmaceutical composition and be administered by a suitable route of administration. [00190] The methods provided herein encompass administering pharmaceutical compositions comprising at least one conjugate provided herein and one or more compatible and pharmaceutically acceptable carriers. In this context, the term “pharmaceutically acceptable” means approved by a regulatory agency of the Federal or state government, or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and in certain embodiments in humans. The term “carrier” includes a diluent, adjuvant (e.g., Freund’s adjuvant (complete and incomplete)), excipient, or vehicle with which the therapeutic is administered. Such pharmaceutical carriers can be sterile liquids, such as water and oils including petroleum, animal, vegetable, or oils of synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, and the like. Water can be used as a carrier when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Examples of suitable pharmaceutical carriers are described in Martin, E.W., Remington’s Pharmaceutical Sciences. [00191] In clinical practice the pharmaceutical compositions or conjugates provided herein may be administered by any route known in the art. Exemplary routes of administration include, but are not limited to, inhalation, intraarterial, intradermal, intramuscular, intraperitoneal, intravenous, nasal, parenteral, pulmonary, and subcutaneous routes. In some embodiments, a pharmaceutical composition or conjugate provided herein is administered parenterally. [00192] The compositions for parenteral administration can be emulsions or sterile solutions. Parenteral compositions may include, for example, propylene glycol, polyethylene glycol, vegetable oils, and injectable organic esters (e.g., ethyl oleate). These compositions can also contain wetting, isotonizing, emulsifying, dispersing, and stabilizing agents. Sterilization can be carried out in several ways, for example, using a bacteriological filter, via radiation, or via heating. Parenteral compositions can also be prepared in the form of sterile solid compositions which can be dissolved at the time of use in sterile water or any other injectable sterile medium. [00193] In some embodiments, a composition provided herein is a pharmaceutical composition or a single unit dosage form. Pharmaceutical compositions and single unit dosage forms provided herein comprise a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic conjugates. [00194] The pharmaceutical composition may comprise one or more pharmaceutical excipients. Any suitable pharmaceutical excipient may be used, wherein a person of ordinary skill in the art is capable of selecting suitable pharmaceutical excipients. Non-limiting examples of suitable excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene glycol, water, ethanol, and the like. Whether a particular excipient is suitable for incorporation into a pharmaceutical composition or dosage form depends on a variety of factors well known in the art including, but not limited to, the way in which the dosage form will be administered to a subject and the specific conjugate in the dosage form. The composition or single unit dosage form, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. Accordingly, the pharmaceutical excipients provided below are intended to be illustrative, and not limiting. Additional pharmaceutical excipients include, for example, those described in the Handbook of Pharmaceutical Excipients, Rowe et al. (Eds.) 6th Ed. (2009), incorporated by reference herein in its entirety. [00195] In some embodiments, the pharmaceutical composition comprises an anti- foaming agent. Any suitable anti-foaming agent may be used. In some aspects, the anti- foaming agent is selected from an alcohol, an ether, an oil, a wax, a silicone, a surfactant, and combinations thereof. In some aspects, the anti-foaming agent is selected from a mineral oil, a vegetable oil, ethylene bis stearamide, a paraffin wax, an ester wax, a fatty alcohol wax, a long- chain fatty alcohol, a fatty acid soap, a fatty acid ester, a silicon glycol, a fluorosilicone, a polyethylene glycol-polypropylene glycol copolymer, polydimethylsiloxane-silicon dioxide, ether, octyl alcohol, capryl alcohol, sorbitan trioleate, ethyl alcohol, 2-ethyl-hexanol, dimethicone, oleyl alcohol, simethicone, and combinations thereof. [00196] In some embodiments, the pharmaceutical composition comprises a co-solvent. Illustrative examples of co-solvents include ethanol, poly(ethylene) glycol, butylene glycol, dimethylacetamide, glycerin, and propylene glycol. [00197] In some embodiments, the pharmaceutical composition comprises a buffer. Illustrative examples of buffers include acetate, borate, carbonate, lactate, malate, phosphate, citrate, hydroxide, diethanolamine, monoethanolamine, glycine, methionine, guar gum, and monosodium glutamate. [00198] In some embodiments, the pharmaceutical composition comprises a carrier or filler. Illustrative examples of carriers or fillers include lactose, maltodextrin, mannitol, sorbitol, chitosan, stearic acid, xanthan gum, and guar gum. [00199] In some embodiments, the pharmaceutical composition comprises a surfactant. Illustrative examples of surfactants include d-alpha tocopherol, benzalkonium chloride, benzethonium chloride, cetrimide, cetylpyridinium chloride, docusate sodium, glyceryl behenate, glyceryl monooleate, lauric acid, macrogol 15 hydroxystearate, myristyl alcohol, phospholipids, polyoxyethylene alkyl ethers, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, polyoxylglycerides, sodium lauryl sulfate, sorbitan esters, and vitamin E polyethylene(glycol) succinate. [00200] In some embodiments, the pharmaceutical composition comprises an anti- caking agent. Illustrative examples of anti-caking agents include calcium phosphate (tribasic), hydroxymethyl cellulose, hydroxypropyl cellulose, and magnesium oxide. [00201] Other excipients that may be used with the pharmaceutical compositions include, for example, albumin, antioxidants, antibacterial agents, antifungal agents, bioabsorbable polymers, chelating agents, controlled release agents, diluents, dispersing agents, dissolution enhancers, emulsifying agents, gelling agents, ointment bases, penetration enhancers, preservatives, solubilizing agents, solvents, stabilizing agents, and sugars. Specific examples of each of these agents are described, for example, in the Handbook of Pharmaceutical Excipients, Rowe et al. (Eds.) 6th Ed. (2009), The Pharmaceutical Press, incorporated by reference herein in its entirety. [00202] In some embodiments, the pharmaceutical composition comprises a solvent. In some aspects, the solvent is saline solution, such as a sterile isotonic saline solution or dextrose solution. In some aspects, the solvent is water for injection. [00203] In some embodiments, the pharmaceutical compositions are in a particulate form, such as a microparticle or a nanoparticle. Microparticles and nanoparticles may be formed from any suitable material, such as a polymer or a lipid. In some aspects, the microparticles or nanoparticles are micelles, liposomes, or polymersomes. [00204] Further provided herein are anhydrous pharmaceutical compositions and dosage forms comprising a conjugate, since, in some embodiments, water can facilitate the degradation of some antibodies or antigen binding fragments thereof. [00205] Anhydrous pharmaceutical compositions and dosage forms provided herein can be prepared using anhydrous or low moisture containing ingredients and low moisture or low humidity conditions. Pharmaceutical compositions and dosage forms that comprise lactose and at least one active ingredient that comprises a primary or secondary amine can be anhydrous if substantial contact with moisture and/or humidity during manufacturing, packaging, and/or storage is expected. [00206] An anhydrous pharmaceutical composition can be prepared and stored such that its anhydrous nature is maintained. Accordingly, anhydrous compositions can be packaged using materials known to prevent exposure to water such that they can be included in suitable formulary kits. Examples of suitable packaging include, but are not limited to, hermetically sealed foils, plastics, unit dose containers (e.g., vials), blister packs, and strip packs. [00207] Lactose-free compositions provided herein can comprise excipients that are well known in the art and are listed, for example, in the U.S. Pharmocopeia (USP) SP (XXI)/NF (XVI). In general, lactose-free compositions comprise an active ingredient, a binder/filler, and a lubricant in pharmaceutically compatible and pharmaceutically acceptable amounts. Exemplary lactose-free dosage forms comprise an active ingredient, microcrystalline cellulose, pre gelatinized starch, and magnesium stearate. [00208] Also provided are pharmaceutical compositions and dosage forms that comprise one or more excipients that reduce the rate by which a conjugate will decompose. Such excipients, which are referred to herein as “stabilizers,” include, but are not limited to, antioxidants such as ascorbic acid, pH buffers, or salt buffers. Parenteral Dosage Forms [00209] In certain embodiments, provided are parenteral dosage forms. Parenteral dosage forms can be administered to subjects by various routes including, but not limited to, subcutaneous, intravenous (including bolus injection), intramuscular, and intraarterial. Because their administration typically bypasses subjects’ natural defenses against contaminants, parenteral dosage forms are typically sterile or capable of being sterilized prior to administration to a subject. Examples of parenteral dosage forms include, but are not limited to, solutions ready for injection, dry products ready to be dissolved or suspended in a pharmaceutically acceptable vehicle for injection, suspensions ready for injection, and emulsions. [00210] Suitable vehicles that can be used to provide parenteral dosage forms are well known to those skilled in the art. Examples include, but are not limited to Water for Injection USP; aqueous vehicles such as, but not limited to, Sodium Chloride Injection, Ringer’s Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, and Lactated Ringer’s Injection; water miscible vehicles such as, but not limited to, ethyl alcohol, polyethylene glycol, and polypropylene glycol; and non-aqueous vehicles such as, but not limited to, corn oil, cottonseed oil, peanut oil, sesame oil, ethyl oleate, isopropyl myristate, and benzyl benzoate. [00211] Excipients that increase the solubility of one or more of the antibodies disclosed herein can also be incorporated into the parenteral dosage forms. Dosage and Unit Dosage Forms [00212] In human therapeutics, the doctor will determine the posology which he considers most appropriate according to a preventive or curative treatment and according to the age, weight, condition, and other factors specific to the subject to be treated. [00213] In certain embodiments, a composition provided herein is a pharmaceutical composition or a single unit dosage form. Pharmaceutical compositions and single unit dosage forms provided herein comprise a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic antibodies or antigen binding fragments thereof. [00214] The amount of the conjugate or composition which will be effective in the prevention or treatment of a disorder or one or more symptoms thereof will vary with the nature and severity of the disease or condition, and the route by which the conjugate is administered. The frequency and dosage will also vary according to factors specific for each subject depending on the specific therapy (e.g., therapeutic or prophylactic agents) administered, the severity of the disorder, disease, or condition, the route of administration, as well as age, body, weight, response, and the past medical history of the subject. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems. [00215] In certain embodiments, exemplary doses of a composition include milligram or microgram amounts of the conjugate per kilogram of subject or sample weight (e.g., about 10 micrograms per kilogram to about 50 milligrams per kilogram, about 100 micrograms per kilogram to about 25 milligrams per kilogram, or about 100 microgram per kilogram to about 10 milligrams per kilogram). In certain embodiments, the dosage of the conjugate provided herein, based on weight of the conjugate, administered to prevent, treat, manage, or ameliorate a disorder, or one or more symptoms thereof in a subject is 0.1 mg/kg, 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 10 mg/kg, or 15 mg/kg or more of a subject’s body weight. In another embodiment, the dosage of the composition or a composition provided herein administered to prevent, treat, manage, or ameliorate a disorder, or one or more symptoms thereof in a subject is 0.1 mg to 200 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 0.1 mg to 20 mg, 0.1 mg to 15 mg, 0.1 mg to 10 mg, 0.1 mg to 7.5 mg, 0.1 mg to 5 mg, 0.1 to 2.5 mg, 0.25 mg to 20 mg, 0.25 to 15 mg, 0.25 to 12 mg, 0.25 to 10 mg, 0.25 mg to 7.5 mg, 0.25 mg to 5 mg, 0.25 mg to 2.5 mg, 0.5 mg to 20 mg, 0.5 to 15 mg, 0.5 to 12 mg, 0.5 to 10 mg, 0.5 mg to 7.5 mg, 0.5 mg to 5 mg, 0.5 mg to 2.5 mg, 1 mg to 20 mg, 1 mg to 15 mg, 1 mg to 12 mg, 1 mg to 10 mg, 1 mg to 7.5 mg, 1 mg to 5 mg, or 1 mg to 2.5 mg. [00216] The dose can be administered according to a suitable schedule, for example, once, two times, three times, or for times weekly. It may be necessary to use dosages of the conjugate outside the ranges disclosed herein in some cases, as will be apparent to those of ordinary skill in the art. Furthermore, it is noted that the clinician or treating physician will know how and when to interrupt, adjust, or terminate therapy in conjunction with subject response. [00217] Different therapeutically effective amounts may be applicable for different diseases and conditions, as will be readily known by those of ordinary skill in the art. Similarly, amounts sufficient to prevent, manage, treat, or ameliorate such disorders, but insufficient to cause, or sufficient to reduce, adverse effects associated with the antibodies or antigen binding fragments thereof provided herein are also encompassed by the described dosage amounts and dose frequency schedules herein. Further, when a subject is administered multiple dosages of a composition provided herein, not all of the dosages need be the same. For example, the dosage administered to the subject may be increased to improve the prophylactic or therapeutic effect of the composition or it may be decreased to reduce one or more side effects that a particular subject is experiencing. [00218] In certain embodiments, treatment or prevention can be initiated with one or more loading doses of a conjugate or composition provided herein followed by one or more maintenance doses. [00219] In certain embodiments, a dose of a conjugate or composition provided herein can be administered to achieve a steady-state concentration of the conjugate in blood or serum of the subject. The steady-state concentration can be determined by measurement according to techniques available to those of skill or can be based on the physical characteristics of the subject such as height, weight, and age. [00220] In certain embodiments, administration of the same composition may be repeated and the administrations may be separated by at least one day, two days, three days, five days, ten days, fifteen days, thirty days, forty-five days, two months, seventy-five days, three months, or six months. In other embodiments, administration of the same prophylactic or therapeutic agent may be repeated and the administration may be separated by at least one day, two days, three days, five days, ten days, fifteen days, thirty days, forty-five days, two months, seventy-five days, three months, or six months. Therapeutic Applications [00221] For therapeutic applications, the conjugates are administered to a mammal, in certain embodiments, a human, in a pharmaceutically acceptable dosage form such as those known in the art and those discussed herein. For example, the conjugates of this disclosure may be administered to a human intravenously as a bolus or by continuous infusion over a period of time, by intramuscular, intraperitoneal, intra-cerebrospinal, subcutaneous, intra- articular, intrasynovial, intrathecal, or intratumoral routes. The conjugates also are suitably administered by peritumoral, intralesional, or perilesional routes, to exert local as well as systemic therapeutic effects. The intraperitoneal route may be particularly useful, for example, in the treatment of ovarian tumors. [00222] The conjugates provided herein may be useful for the treatment of any disease or condition described herein (e.g., inflammatory and/or proliferative disease or condition). In some embodiments, the disease or condition is a disease or condition that can be diagnosed by overexpression of an antigen. In some embodiments, the disease or condition is a disease or condition that can benefit from treatment with an macromolecule. In some embodiments, the disease or condition is a cancer. [00223] Any suitable cancer may be treated with the conjugates provided herein. Exemplary or suitable cancers include, for example, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), adrenocortical carcinoma, anal cancer, appendix cancer, astrocytoma, basal cell carcinoma, brain tumor, bile duct cancer, bladder cancer, bone cancer, breast cancer, bronchial tumor, carcinoma of unknown primary origin, cardiac tumor, cervical cancer, chordoma, colon cancer, colorectal cancer, craniopharyngioma, ductal carcinoma, embryonal tumor, endometrial cancer, ependymoma, esophageal cancer, esthesioneuroblastoma, fibrous histiocytoma, Ewing sarcoma, eye cancer, germ cell tumor, gallbladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, gestational trophoblastic disease, glioma, head and neck cancer, hepatocellular cancer, histiocytosis, Hodgkin lymphoma, hypopharyngeal cancer, intraocular melanoma, islet cell tumor, Kaposi sarcoma, kidney cancer, Langerhans cell histiocytosis, laryngeal cancer, lip and oral cavity cancer, liver cancer, lobular carcinoma in situ, lung cancer, macroglobulinemia, malignant fibrous histiocytoma, melanoma, Merkel cell carcinoma, mesothelioma, metastatic squamous neck cancer with occult primary, midline tract carcinoma involving NUT gene, mouth cancer, multiple endocrine neoplasia syndrome, multiple myeloma, mycosis fungoides, myelodysplastic syndrome, myelodysplastic/myeloproliferative neoplasm, nasal cavity and par nasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-small cell lung cancer, oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, papillomatosis, paraganglioma, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytomas, pituitary tumor, pleuropulmonary blastoma, primary central nervous system lymphoma, prostate cancer, rectal cancer, renal cell cancer, renal pelvis and ureter cancer, retinoblastoma, rhabdoid tumor, salivary gland cancer, Sezary syndrome, skin cancer, small cell lung cancer, small intestine cancer, soft tissue sarcoma, spinal cord tumor, stomach cancer, T-cell lymphoma, teratoid tumor, testicular cancer, throat cancer, thymoma and thymic carcinoma, thyroid cancer, urethral cancer, uterine cancer, vaginal cancer, vulvar cancer, and Wilms tumor. [00224] In some embodiments, the disease to be treated with the conjugates provided herein is gastric cancer, colorectal cancer, renal cell carcinoma, cervical cancer, non-small cell lung carcinoma, ovarian cancer, uterine cancer, endometrial carcinoma, prostate cancer, breast cancer, head and neck cancer, brain carcinoma, liver cancer, pancreatic cancer, mesothelioma, and/or a cancer of epithelial origin. In one embodiment, the disease is colorectal cancer. In one embodiment, the disease is ovarian cancer. In one embodiment, the disease is breast cancer. In one embodiment, the disease is lung cancer. In one embodiment, the disease is head and neck cancer. In one embodiment, the disease is renal cell carcinoma. In one embodiment, the disease is brain carcinoma. In one embodiment, the disease is endometrial carcinoma. In particular embodiments, the disease is pancreatic cancer, multiple myeloma, colorectal cancer, renal and mammary carcinomas, skin cancer, and/or cervical intraepithelial neoplasia. [00225] In particular embodiments, the disease is non-Hodgkin’s lymphoma, pancreatic cancer, multiple myeloma, colorectal cancer, renal and mammary carcinomas, skin cancer, and/or cervical intraepithelial neoplasia. [00226] In certain embodiments, provided herein are methods for the treatment of cancer that include the administration of an effective amount of conjugates provided herein, or a pharmaceutically acceptable salt thereof. In certain embodiments, provided herein are methods for treating cancer in a subject. In certain embodiments, the methods encompass the step of administering to the subject in need thereof an amount of a conjugate described herein effective for the treatment of cancer in combination with a second agent effective for the treatment or prevention of the infection. In certain embodiments, the conjugate is in the form of a pharmaceutical composition or dosage form, as described elsewhere herein. [00227] In certain embodiments, the subject is a treatment naïve subject. In further embodiments, the subject has previously received therapy for a cancer. For instance, in certain embodiments, the subject has not responded to a single agent treatment regimen. [00228] In certain embodiments, the subject is a subject that discontinued some other therapy because of one or more adverse events associated with the other therapy. [00229] In certain embodiments, the subject has received some other anti-cancer therapy and discontinued that therapy prior to administration of a method provided herein. In further embodiments, the subject has received therapy and continues to receive that therapy along with administration of a conjugate provided herein. The conjugates described herein can be co- administered with other therapy for treatment of cancer according to the judgment of one of skill in the art. In certain embodiments, the methods or compositions provided herein can be co-administered with a reduced dose of the other therapy for the treatment of cancer. [00230] In certain embodiments, provided are methods of treating a subject that is refractory to treatment with some other anti-cancer agent. In some embodiments, the subject can be a subject that has responded poorly to some other anti-cancer treatment. Diagnostic Applications [00231] In some embodiments, the conjugates provided herein are used in diagnostic applications. These assays may be useful, for example, in making a diagnosis and/or prognosis for a disease, such as a cancer. [00232] In some diagnostic and prognostic applications or embodiments, the conjugate may be labeled with a detectable moiety. Suitable detectable moieties include, but are not limited to, radioisotopes, fluorescent labels, and enzyme-substrate labels. In another embodiment, the conjugate need not be labeled, and the presence of the conjugate can be detected using a labeled antibody or antigen binding fragment thereof which specifically binds to the conjugate. Kits [00233] In some embodiments, a conjugate provided herein is provided in the form of a kit (i.e., a packaged combination of reagents in predetermined amounts with instructions for performing a procedure). In some embodiments, the procedure is a diagnostic assay. In certain embodiments, the procedure is a therapeutic procedure. [00234] In some embodiments, the kit further comprises a solvent for the reconstitution of the conjugate. In some embodiments, the conjugate is provided in the form of a pharmaceutical composition. [00235] In some embodiments, the kits can include a conjugate or composition provided herein, an optional second agent or composition, and instructions providing information to a health care provider regarding usage for treating the disorder. Instructions may be provided in printed form or in the form of an electronic medium such as a floppy disc, CD, or DVD, or in the form of a website address where such instructions may be obtained. A unit dose of a conjugate or a composition provided herein, or a second agent or composition, can include a dosage such that when administered to a subject, a therapeutically or prophylactically effective plasma level of the compound or composition can be maintained in the subject for at least one day. In some embodiments, a compound or composition can be included as a sterile aqueous pharmaceutical composition or dry powder (e.g., lyophilized) composition. [00236] In some embodiments, suitable packaging is provided. As used herein, “packaging” includes a solid matrix or material customarily used in a system and capable of holding within fixed limits a compound provided herein and/or a second agent suitable for administration to a subject. Such materials include glass and plastic (e.g., polyethylene, polypropylene, and polycarbonate) bottles, vials, paper, plastic, plastic-foil laminated envelopes, and the like. If e-beam sterilization techniques are employed, the packaging should have sufficiently low density to permit sterilization of the contents. Preparation and Synthetic Procedures [00237] Provided below is a general scheme for the synthesis of compounds of Formula (I), where PG is a nitrogen-protecting group, for example, in certain embodiments, Boc; and all h ibl dfi d i h S i bdi h i

Conjugation [00238] The conjugates can be prepared by standard techniques. In certain embodiments, a macromolecule is contacted with a fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound under conditions suitable for forming a bond from the macromolecule to the fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound to form a conjugate. In certain embodiments, a macromolecule is contacted with a linker precursor under conditions suitable for forming a bond from the macromolecule to the linker. The resulting macromolecule-linker is contacted with a fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound under conditions suitable for forming a bond from the macromolecule-linker to the fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound to form a conjugate. In certain embodiments, a fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound is contacted with a linker precursor under conditions suitable for forming a bond from the fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound to the linker. The resulting fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound-linker is contacted with a macromolecule under conditions suitable for forming a bond from the fluorenylmethoxycarbonyl and/or fluorenylmethylaminocarbonyl compound-linker to the macromolecule to form a conjugate. Suitable linkers for preparing the conjugates are disclosed herein, and exemplary conditions for conjugation are described in the Examples below. EXAMPLES [00239] The compounds provided herein can be prepared, isolated, or obtained by any method apparent to those of skill in the art. Compounds provided herein can be prepared according to the Exemplary Preparation Schemes provided below. Reaction conditions, steps, and reactants not provided in the Exemplary Preparation Schemes would be apparent to, and known by, those skilled in the art. As used herein, the symbols and conventions used in these processes, schemes and examples, regardless of whether a particular abbreviation is specifically defined, are consistent with those used in the contemporary scientific literature, for example, the Journal of the American Chemical Society or the Journal of Biological Chemistry. Specifically, but without limitation, the following abbreviations may be used in the examples and throughout the specification: g (grams); mg (milligrams); mL (milliliters); ^L (microliters); mM (millimolar); ^M (micromolar); Hz (Hertz); MHz (megahertz); mmol (millimoles); h, hr, or hrs (hours); min (minutes); MS (mass spectrometry); ESI (electrospray ionization); TLC (thin layer chromatography); HPLC (high pressure liquid chromatography); rt (room temperature); atm (atmospheres); calcd (calculated); equiv (equivalents); BBN (9- borabicyclo[3.3.1]nonane); CDCl 3 (deuterated chloroform); DBCO (dibenzocyclooctyne- amine); DCE (dichloroethane); DCM (dichloromethane); DIPEA (diisopropylethylamine); DMSO (dimethylsulfoxide); DMSO-d 6 (deuterated dimethylsulfoxide); dppf ([1,1′- Bis(diphenylphosphino)ferrocene]dichloronickel(II)); EtOAc (ethyl acetate); EtOH (ethanol); MeCN (acetonitrile); MeOH (methanol); RB (round-bottomed flask); TFA (trifluoroacetic acid); THF (tetrahydrofuran); DMF (dimethylformamide); and BOC (t-butyloxycarbonyl). [00240] For all of the following examples, standard workup and purification methods known to those skilled in the art can be utilized. Unless otherwise indicated, all temperatures are expressed in °C (degrees Celsius). All reactions are conducted at room temperature unless otherwise noted. Synthetic methodologies illustrated herein are intended to exemplify the applicable chemistry through the use of specific examples and are not indicative of the scope of the disclosure. Example 1 Preparation of Compound A [00241] Preparation of 9-formyl-9H-fluorene-2-carboxylic acid (Compound 2) [00242] To an oven-dried 250 mL RB flask equipped with a magnetic stir bar, was added 9H-fluorene-2-carboxylic acid 1 (5 g, 23.78 mmol) and anhydrous DMSO (60 mL). The slurry was flushed with argon, and ethyl formate (32.52 mL, 404.32 mmol) and potassium tert- butoxide (21.35 g, 190.27 mmol) were added sequentially at room temperature. The reaction was stirred at room temperature for 3-4 h under nitrogen, after which the reaction was quenched by the addition of HCl to pH 2. Solvent was removed, and the aqueous was extracted with EtOAc. The organics were washed with brine, dried over Na2SO4, and concentrated. The solids were washed with Hexane and MeOH, and dried under vacuum. LCMS (ESI) m/z 239.1 (M+H). [00243] Preparation of 9-(hydroxymethyl)-9H-fluorene-2-carboxylic acid) (Compound 3) [00244] To an oven-dried 250 mL RB flask equipped with a magnetic stir bar, was added Compound 2 (4.5 g, 18.89 mmol), anhydrous THF (10 mL), and water (100 mL). The slurry was cooled to 0 °C with an ice bath. NaBH4 (7.2 g, 190.27 mmol) was added carefully to the mixture over a period of 20 min. The reaction was slowly warmed to room temperature and stirred at room temperature for 2 h under N2 atm. Thereafter, the reaction was cooled to 0 °C and then carefully quenched by the addition of cold HCl to pH 2. Solids were formed. The solids were filtered and washed with hexane and MTBE, purified by reverse phase preparative HPLC, and then dried under vacuum. Compound 3 (2.9 g, 12.07 mmol, 51.1% yield) was obtained as off white solid. LCMS (ESI) m/z 241.1 (M+H). 1 H NMR (400 MHz, DMSO-d 6 ): δ 12.87 (s, 1H), 8.26-8.25 (m, 1H), 8.00-7.95 (m, 3H), 7.71-7.69 (m, 1H), 7.44-7.42 (m, 1H), 5.13 (t, J = 5.20 Hz, 1H), 4.09 (t, J = 6.80 Hz, 1H), 3.93-3.88 (m, 1H), 3.70-3.65 (m, 1H). [00245] Synthesis of PEGylated Fmoc DBCO linker (Compound A ) [00246] Scheme 2

[00247] Synthesis of Compound 4 (PEGylation of Compound 3) To an oven-dried 500 mL flask equipped with a magnetic stir bar, was added mPEG-NH 2 (20,000) (MW = 19200) (23.98 g, 1.2 mmol) in anhydrous toluene (250 mL). The mixture was azeotropically dried under reduced pressure at 45 °C on a rotary evaporator, lyophilized overnight, and then dissolved in anhydrous DCM (200 mL). A solution of 9-(hydroxymethyl)- 9H-fluorene-2-carboxylic acid (Compound 3) (0.72 g, 2.99 mmol) and HOBt (0.61 g, 4.5 mmol) was dissolved in anhydrous DMF (15 mL) and added to the mPEG-NH 2 (20,000) solution. Thereafter, DCC (0.93 g, 4.5 mmol) was added. The reaction was stirred at rt for one day under N 2 atm. Reaction progress was monitored by analytical HPLC-ELSD (Column: Jupiter C4: LC column 250 mm × 4.6 mm × 5µm (Vendor: Phenomenex, part # 00G167-E0), Mobile Phase: Acetonitrile and Water with 0.1% TFA (90% water to 10% water in 50 min, flow rate, 1 mL/min). Thereafter, HPLC showed completion of the reaction, solvents were removed under reduced pressure, and the crude PEG product was added to isopropanol (600 mL) with gentle heating (35 °C). To this was added 200 mL MTBE and then the mixture was cooled to 10 °C. Solids were filtered and washed with cold IPA (100 mL) and MTBA (50 mL). Crude mono-PEGylated amide 4 as off-white solids were dried under vacuum. The PEGylated amide 4 was dissolved in DCM (300 mL), added to a capto S resin (prewashed with water; 1 L), and stirred overnight. After filtration, the solvent was entirely removed. MALDI-TOF, 1 H NMR, and HPLC-ELSD confirmed the desired Compound 4 in good purity. Step 2: Final DBCO Acylation of mono-PEGylated Fmoc Compound 4 [00248] To an oven-dried 250 mL flask equipped with a magnetic stir bar, were added Fmoc PEGylated Compound 4 (11.4 g, 0.52 mmol) (azeotropically dried with 100 mL toluene removed at 50 °C under vacuum prior to use), and anhydrous DCM (70 mL). The clear solution was flushed with argon and then triphosgene (231.9 mg, 0.78 mmol) and pyridine (0.06 mL, 0.73 mmol) were added sequentially. The reaction mixture was stirred at room temperature for 2 h under nitrogen. DCM and pyridine were removed under reduced pressure. The chloroformate intermediate 4a was dissolved in 50 mL of DCM, and DBCO amine (432 mg, 1.56 mmol) was added in one portion. The reaction was stirred at room temperature for 2 h under N2 atm. Solvent was removed to dryness, the solids were dissolved in 15 mL of DCM and precipitated via IPA (500 mL). The precipitation was repeated twice. Solids were filtered and dried under vacuum. Compound A was confirmed by 1 H NMR (CDCl3), MALDI-TOF, SDS-PAGE, and analytical ELSD-HPLC. Purity analysis was checked via the above mentioned analytical method. Example 2 Preparation of Compound 13 [00249] Scheme 3 [00250] Synthesis of 7-methoxy-9H-fluorene-2-carboxylic acid (Compound 9) [0 y es s o o pou [00252] To a stirred solution of 9H-fluoren-2-amine 5 (50 g, 0.276 mol) in acetic acid (400 mL) was added concentrated sulfuric acid (50 mL) at room temperature. The solution became turbid. Water (50 mL) was added, and the reaction mixture was cooled to 0 °C. Sodium nitrite solution (19 g, 0.275 mol, in 80 mL water) was added drop wise at 0 o C. The reaction mixture was stirred for 30 min at the same temperature. A hot solution of 10% sulfuric acid 1300 mL (70 °C) was added slowly to the reaction mixture and stirred at 100 °C for 5 h. Progress of the reaction was monitored by TLC. After completion, the reaction was cooled to room temperature. A solid precipitated out and was filtered and washed with water (250 mL). The solid was dried to obtain 48.6 g of 9H-fluoren-2-ol (6), Yield: 48.6 g, 97.2%, Mass by GCMS: 182.1. 1 H-NMR (400 MHz, DMSO-d6): δ 9.48 (s, 1H), 8.44 (dd, J = 8.00, 18.80 Hz, 2H), 7.49 (d, J = 7.20 Hz, 1H), 7.31 (t, J = 7.20 Hz, 1H), 7.19 (t, J = 7.60 Hz, 1H), 6.98 (d, J = 2.00 Hz, 1H), 6.79 (dd, J = 1.60, 8.40 Hz, 2H), 3.81 (s, 2H). [00253] Synthesis of compound 7 [00254] To a stirred solution of compound 6 (48.6 g, 0.267 mmol) in anhydrous DMF (250 mL) was added K2CO3 (100 g, 0.774 mol., 2.9 equiv) followed by methyl iodide (33 mL, 0.534 mol) at room temperature. The reaction mixture was stirred at room temperature for 12 h. Progress of the reaction was monitored by thin layer chromatography. After completion, the reaction mixture was cooled to 0 °C and quenched using ice-cold water (500 mL). Solids precipitated during quenching were allowed to stir for 15 min at the same temperature. The solids were filtered and washed with water (250 mL). The solids were dried to obtain 2- methoxy-9H-fluorene 7. Yield: 41 g , 78%. Mass by GCMS: found 196.1. 1 H NMR (400 MHz, DMSO-d 6 ): δ 7.79 (dd, J = 1.60, 7.80 Hz, 2H), 7.53 (d, J = 7.60 Hz, 1H), 7.34 (t, J = 7.60 Hz, 1H), 7.25-7.19 (m, 2H), 6.96 (dd, J = 2.40, 8.40 Hz, 1H), 3.88 (s, 2H), 3.82 (s, 3H). [00255] Synthesis of Compound 8 [00256] A stirred solution of compound 7 (41 g, 0.209 mol) in DCE (500 mL) was cooled to 0 °C. AlCl3 (30.68 g, 0.23 mol) and acetyl chloride (18 g, 0.23 mol) were added into the reaction mixture at 0 °C. The reaction mixture was heated to 45 °C and stirred for 1 h. Reaction progress was monitored by thin layer chromatography. After completion, the reaction mixture was cooled to 0 °C and quenched using 2 M HCl (100 mL). DCM (200 mL) was added into the reaction mixture. The aqueous layer was extracted twice with DCM (200 mL each). The organic layer was dried over Na2SO4 and distilled out completely to obtain crude compound. Crude compound was taken in ethanol (10 vol), stirred for 20 min, filtered, and dried under vacuum to obtain 43.19 g of 1-(7-methoxy-9H-fluoren-2-yl) ethan-1-one 8. Yield: 43.19 g, 88%. Mass by LCMS [M+1]: found 239.2. 1 H NMR (400 MHz, DMSO-d 6 ): δ 8.13 (s, 1H), 7.99 (dd, J = 1.60, 8.00 Hz, 1H), 7.92 (d, J = 8.00 Hz, 2H), 7.25 (d, J = 2.00 Hz, 1H), 7.02 (dd, J = 2.40, 8.40 Hz, 1H), 3.98 (s, 2H), 3.84 (s, 3H), 2.61 (s, 3H). [00257] Synthesis of Compound 9 [00258] To a stirred solution of compound 8 (10 g, 0.042 mol) in 1,4-dioxane (200 mL) was added a freshly prepared NaOBr solution (NaOH (28.7 g) + ice water (130 mL) + bromine (10 mL)) at 0 °C. The reaction mixture was heated to 45 °C and stirred for 30 min. Progress of the reaction was monitored by thin layer chromatography. After completion, the reaction mixture was cooled to 0 °C and quenched with ice-cold water (100 mL). The reaction mixture was acidified using 1.5 N HCl to pH 2. Solids precipitated out during quenching and were allowed to stir for 15 min. The solids were filtered and washed with water (185 mL). Solid compound was taken in ethanol (3 vol), stirred for 20 min, filtered, and dried under vacuum to obtain 7-methoxy-9H-fluorene-2-carboxylic acid 9. Yield: 8.6 g. LCMS [M+1]: found 241.1. [00259] Synthesis of Compound 10 [00260] A stirred solution of compound 9 (8.6 g, 0.035 mol) in DMSO (80 mL) was degassed with N 2 for 10 min. Ethylformate (45.12 g, 0.609 mol) was added into the reaction mixture at room temperature. Potassium tert-butoxide (32.16 g, 0.286 mol) was added into the reaction mixture at room temperature and stirred for 1 h. Progress of the reaction was monitored by thin layer chromatography. After completion, the reaction mixture was cooled to 0 °C and quenched using ice-cold water (100 mL). The reaction mixture was acidified using 1.5 N HCl to pH 4. EtOAc (350 mL) was added into the above reaction mixture. The aqueous layer was extracted twice with EtOAc (100 mL each). The organic layer was dried over Na2SO4 and distilled to obtain (Z)-9-(hydroxymethylene)-7-methoxy-9H-fluorene-2-carboxylic acid 10. Yield: 9.5g. LCMS [M-1]: found 266.9. [00261] Synthesis of Compound 11 [00262] To a stirred solution of compound 10 (9.5 g, 0.0354 mol) in THF (100 mL) was added water (197 mL) at room temperature. The reaction mixture was cooled to 0 °C. Sodium borohydride (4.02 g, 0.106 mol) was added slowly into reaction mixture in portions. The reaction mixture was stirred at room temperature for 1 h. The reaction was monitored by thin layer chromatography. After completion, the reaction mixture was cooled to 0 °C and quenched using 1.5 N HCl to pH 5. The reaction mixture was extracted twice using ethyl acetate (200 mL). The organic layer was dried over Na2SO4, filtered, and distilled out completely to obtain crude 9-(hydroxymethyl)-7-methoxy-9H-fluorene-2-carboxylic acid 11. Crude compound was purified using preparative HPLC to obtain 3.5 g of pure compound 11. LCMS: found 271.2 [M+1]. 1 H NMR (400 MHz, DMSO-d 6 ): δ 12.75 (s, 1H), 8.19 (s, 1H), 7.96 (d, J = 8.00 Hz, 1H), 7.85 (dd, J = 3.60, 8.20 Hz, 2H), 7.28 (s, 1H), 7.01 (dd, J = 2.40, 8.40 Hz, 1H), 5.10 (t, J = 4.80 Hz, 1H), 4.03 (t, J = 6.80 Hz, 1H), 3.92-3.87 (m, 1H), 3.83 (s, 3H), 3.71-3.66 (m, 1H). [0 [00264] Compound 13 was synthesized using the same methods as described above and confirmed by 1 H NMR (CDCl3), MALDI-TOF, SDS-PAGE, and analytical ELSD-HPLC. Example 3 Preparation of Compound 20 [00265] Scheme 5: Synthesis of 4-(9-(hydroxymethyl)-9H-fluoren-2-yl)butanoic acid 18 [ [00267] To a stirred solution of methyl 3-butenoate (3.1 mL, 30.61 mmol) in a 100 mL flask, was added 9-borabicyclononane (9-BBN) (0.5 N in THF) (57.0 mL, 28.56 mmol) under N2 atmosphere, and stirred at room temperature for 3 h.2-bromo-9H-fluorene 14 (5.0 g, 20.40 mmol) was charged in another 250 mL flask with THF (100 mL) and was added to the 9-BBN complex. Sodium methoxide (25% in MeOH) (9.7 mL, 44.88 mmol) was added at 0 °C. Then PdCl 2 (dppf) (745 mg, 1.02 mmol) was added. The reaction mixture was stirred at 65 °C for 3 h. After completion (i.e., the reaction was monitored by thin layer chromatography), the reaction mixture was filtered through the Celite®. The filtrate was diluted with ethyl acetate (300 mL) and washed with water (100 mL). The organic layer was separated. The combined organic layer was dried over Na 2 SO 4 and concentrated to provide crude compound. The crude compound was purified by column chromatography (230-400 mesh) with 10% EtOAc/Hexane to provide desired compound 15 as an off-white solid (3.3 g). 1 H NMR (400 MHz, DMSO-d 6 ): δ 7.77 (d, J = 7.60 Hz, 1H), 7.72 (d, J = 8.00 Hz, 1H), 7.56-7.54 (m, 1H), 7.39 (d, J = 3.60 Hz, 1H), 7.36 (s, 1H), 7.32 (d, J = 1.20 Hz, 1H), 7.20 (d, J = 0.40 Hz, 1H), 3.89 (s, 2H), 3.52 (s, 3H), 2.77-2.44 (m, 2H), 1.92-1.93 (m, 2H), 1.59-1.57 (m, 2H). [00268] Synthesis of Compound 16 [00269] To a stirred solution of compound 15 (3.0 g, 11.27 mmol) in 50 mL of EtOH was added KOH (1.2 g, 22.56 mmol). The reaction mixture was stirred for 6 h at room temperature. The reaction mixture was concentrated under reduced pressure. Crude was diluted with water (100 mL) and acidified with acetic acid (pH ~2). The solids obtained were filtered and dried. Desired compound 16 was obtained (2.3 g) as an off-white solid. 1 H NMR (400 MHz, DMSO-d 6 ): δ 7.77 (d, J = 7.60 Hz, 1H), 7.72 (d, J = 8.00 Hz, 1H), 7.56-7.54 (m, 1H), 7.39 (d, J = 3.60 Hz, 1H), 7.36 (s, 1H), 7.32 (d, J = 1.20 Hz, 1H), 7.20 (d, J = 0.40 Hz, 1H), 3.89 (s, 2H), 2.77-2.44 (m, 2H), 1.92-1.93 (m, 2H), 1.59-1.57 (m,2H). [00270] Synthesis of Compound 17 [00271] To a stirred solution of NaH (60% in mineral oil) (2.28 g, 57.14 mmol, 12.0 equiv) in 20 mL of THF, was added Compound 16 (1.2 g, 4.76 mmol) in THF (20 mL ) and then ethyl formate (15 mL) at 0 °C. The reaction mixture was stirred at 50 °C for 3 h. After completion (by TLC), the reaction mixture was diluted with cold water (15 mL) and acidified with concentrated HCl (pH ~2). The reaction mixture was extracted with ethyl acetate (2x100 mL). The organic layers were separated. The combined organic layer was dried over Na 2 SO 4 and concentrated. Crude was purified by column chromatography using EtOAc/petroleum ether as eluent to obtain compound 17 (520 mg). 1 H NMR (400 MHz, DMSO-d 6 ): δ 12.06 (s, 1H), 11.11 (s, 1H), 7.77 (d, J = 7.60 Hz, 1H), 7.72 (d, J = 8.00 Hz, 1H), 7.56-7.54 (m, 1H), 7.39 (d, J = 3.60 Hz, 1H), 7.36 (s, 1H), 7.32 (d, J = 1.20 Hz, 1H), 7.20 (d, J = 0.40 Hz, 1H), 2.77-2.44 (m, 2H), 1.92-1.93 (m, 2H), 1.59-1.57 (m, 2H). [00272] Synthesis of Compound 18 [00273] To a stirred solution of Compound 17 (1.4 g, 5.0 mmol) in THF (5 mL) and H 2 O (20 mL) cooled to 0 °C, was added NaBH 4 (370 mg, 10.0 mmol) under N 2 atmosphere at 0 °C. The reaction mixture was stirred for 30 min at room temperature. The reaction was monitored by thin layer chromatography. The reaction mixture was diluted with cold water (15 mL) and acidified with concentrated HCl (pH ~ 2). The reaction mixture was extracted with ethyl acetate (2 x 100 mL). The combined organic layer was dried over Na 2 SO 4 and concentrated. Crude was purified by reverse phase column chromatography by using 0.1 % formic acid in water and acetonitrile as eluent. Collected fractions were lyophilized to provide compound 18 as an off-white solid. LCMS: 283.2 [M+1]. 1 H NMR (400 MHz, DMSO-d6): δ 12.06 (s, 1H), δ 7.77 (d, J = 7.60 Hz, 1H), 7.72 (d, J = 8.00 Hz, 1H), 7.56-7.54 (m, 1H), 7.39 (d, J = 3.60 Hz, 1H), 7.36 (s, 1H), 7.32 (d, J = 1.20 Hz, 1H), 7.20 (d, J = 0.40 Hz, 1H), 5.07 (s, 1H), 3.97 (t, J = 6.80 Hz, 1H), 3.74 (d, J = 4.40 Hz, 1H), 2.52-2.67 (m, 2H), 2.24-2.34 (m, 2H), 1.81-1.88 (m, 2H). [00274] Synthesis of Compound 20 [00275] Scheme 6 [00276] Compound 20 was synthesized using same methods as described in Scheme 2. Example 4 Preparation of Compound 28 [00277] Synthesis of (2-(4-aminobutyl)-9H-fluoren-9-yl)methanol 26 [00278] Scheme 7 [0 [0 0280] To a st rred so ut on o 2-bromo-9H- uorene 21 (2.0 g, 8.0 mmo ) n a sealed tube, were added diethyl amine (30 mL) and tert-butyl but-3-yn-1-ylcarbamate (4.0 mL, 24.4 mmol) at room temperature. The resulting reaction mixture was degassed for 10 minutes. PdCl 2 (PPh 3 ) 2 (560 mg, 0.01mmol) and CuI (315 mg, 0.02 mmol) were added. The reaction mixture was stirred at 70 °C for 16 h. After completion (i.e., the reaction was monitored by thin layer chromatography), the reaction mixture was filtered through Celite®. The filtrate was concentrated under reduced pressure to provide crude material, which was purified by column chromatography (230-400 mesh silica) with 5 % EtOAc/hexane to give compound 22 (2.1g, 80 %) as an off-white solid. 1 H NMR (400 MHz, DMSO-d6): δ 7.86-7.92 (m, 2H), 7.60 (s, 1H), 7.58 (s, 1H), 7.40-7.42 (m, 2H), 7.31-7.35 (m, 2H), 7.06(s, 1H), 3.91 (s, 2H), 3.19-3.14 (m, 2H), 2.55-2.50 (m, 2H), 1.4 (s, 9H). [00281] Synthesis of Compound 23 [00282] To a stirred solution of compound 22 (2.1 g, 63.0 mmol) in 90 mL of EtOAc, was added 2.1 g of 10% Pd/C at room temperature. The reaction mixture was stirred at room temperature for 16 h under a H 2 pressure of 10 Kg/cm 2 in an autoclave. Starting material was consumed (observed by LCMS). After completion, the reaction mixture was filtered and the filtrate was concentrated to give compound 23 (1.9 g, 90 %) as an off-white solid. Yield: 1.9 g. 1 H NMR (400 MHz, DMSO-d6): δ 7.86-7.92 (m, 2H), 7.606 (s, 1H), 7.58 (s, 1H), 7.40-7.42 (m, 2H), 7.31-7.35 (m, 2H), 6.81 (s, 1H), 3.87 (s, 1H), 2.97-2.92 (q, 2H), 1.34 (s, 11H). [00283] Synthesis of Compound 24 [00284] To a stirred solution of Compound 23 (3.5 g, 10.38 mmol) in THF (40 mL), were added KO-t-Bu (4.42 g, 112.20 mmol) and ethyl formate (30 mL) at -15 °C. The resulting reaction mixture was stirred at the same temperature for 10 minutes. After completion (by TLC), the reaction was quenched with ice-water (100 mL), and the mixture was diluted and extracted with ethyl acetate (2 x 200 mL). The organic layer was washed with brine (500 mL), dried over anhydrous Na 2 SO 4 , filtered, and concentrated. Compound 24 was used in the next step without further purification. [00285] Synthesis of Compound 25 [00286] To a stirred solution of compound 24 (3.4 g, 9.31 mmol) in 10 mL THF and 30 mL of H2O, were added NaBH4 (1.37 g, 37.26 mmol) under N2 atmosphere at 0 °C. The reaction was stirred at room temperature for 30 min. The reaction mixture was diluted with cold water (50 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic layer was dried over Na2SO4 and concentrated. Crude product was purified by reverse phase column chromatography by using 0.1% formic acid in water and acetonitrile as eluent. Combined fractions were lyophilized to provide compound 25 (1.2 g) as an off-white solid. 1 H NMR (400 MHz, DMSO-d 6 ): δ 7.86-7.92 (m, 2H), 7.60 (s, 1H), 7.58 (s, 1H), 7.40-7.42 (m, 2H), 7.31-7.35 (m, 2H), 6.811 (s, 1H), 5.07-5.05 (t, J = 4.80 Hz, 1H), 3.97-3.94 (t, J = 6.80 Hz, 1H), 3.71- 3.94 (m, 2H), 2.93-2.98 (m, 2H), 2.635-2.616 (t, J = 7.60 Hz, 2H), 1.55-1.61 (m, 2H), 1.37- 1.47 (m, 13H). [00287] Synthesis of Compound 26 [00288] To a stirred solution of Compound 25 (1.2 g, 3.26 mmol) was added 4 M HCl in dioxane (20 mL) under N 2 atmosphere at 0 °C. The reaction mixture was stirred for 2 h at room temperature. The reaction was monitored by thin layer chromatography. The reaction mixture was concentrated under reduced pressure to provide crude, which was further purified by reverse phase HPLC using 0.1% TFA in water and acetonitrile as eluent. Combined fractions were lyophilized to provide compound 26 (1.0 g, 75 %) as a gummy solid. LCMS: found 268.2 [M+1]. 1 H NMR (400 MHz, DMSO-d6): δ 7.86-7.762 (m, 5H), 7.606 (s, 1H), 7.51(s, 1H), 7.31-7.22 (m, 3H), 5.10-5.07 (t, J = 4.80 Hz, 1H), 3.98-3.94 (t, J = 6.80 Hz, 1H), 3.74-3.72 (t, J = 6.40 Hz, 2H), 2.66-2.83 (m, 4H), 1.70-1.56 (m, 4H). [00289] Synthesis of Compound 28 [00290] Scheme 8 [00291] Compound 28 was synthesized using same methods as described in Scheme 2. Example 5 [00292] Bis PEGylated N-acetyl-DBCO linker Example 6 [00293] Bis PEGylated N-sulfonamide-DBCO linker

Example 7 [00294] Aminooxy PEGylated Fmoc linkers for oxime ligation [00295] Scheme 9 [00296] Aminooxy mono PEGylated Fmoc linker 1 was synthesized as described above and Boc deprotected by treating with 4M HCl in dioxane. The product was purified by reverse phase preparative HPLC and confirmed by 1 H NMR (CDCl3), MALDI-TOF, SDS-PAGE, and analytical ELSD-HPLC. Example 8 Conjugation of Compound A [00297] A 5 mM stock solution of compound A was mixed with a final concentration of 1-50 mg/mL cytokine, antibody, or any protein incorporated with pAMF (nnAA) in 1xPBS at a Compound A to pAMF ratio of 2-50. The conjugation reaction mixture was incubated at 30 °C overnight. The conjugation efficiency was measured by SDS-PAGE. Unconjugated compound A is removed by cation exchange. PEGylated protein conjugates are formulated in 10 mM citric acid, pH 4.5 buffer, and stored at -80 °C. [00298] PEG release: To release the PEG from the compound A conjugate, the compound A conjugate was buffer exchanged into 100 mM sodium bicarbonate buffer at pH 9.0 and incubated at 30 °C overnight. The released product was analyzed on SDS-PAGE (FIG.3). [00299] Conjugation of Aminooxy mono PEGylated Fmoc linker 1: 50 mM stock solution of Aminooxy mono PEGylated Fmoc linker 1 was mixed with a final concentration of 1-50 mg/mL protein incorporated with pAcF (non-natural Amino acid) in 100 mM sodium acetate buffer at pH 4.5 at an Aminooxy mono PEGylated Fmoc linker 1:pAcF ratio of 2-50. The conjugation reaction mixture was incubated at 30 °C for 1-3 days. The conjugation efficiency was measured by SDS-PAGE (FIG.4). Unconjugated PEG was removed by cation exchange. PEGylated proteins were formulated in 10 mM citric acid, pH 4.5 buffer and stored at -80 °C. 1.1 Equivalents [00300] The disclosure set forth above may encompass multiple distinct embodiments with independent utility. Although each of these embodiments has been disclosed, the specific embodiments thereof as disclosed and illustrated herein are not to be considered in a limiting sense, because numerous variations are possible. The subject matter of the embodiments includes all novel and nonobvious combinations and subcombinations of the various elements, features, functions, and/or properties disclosed herein. The following claims particularly point out certain combinations and subcombinations regarded as novel and nonobvious. Alternative embodiments as in other combinations and subcombinations of features, functions, elements, and/or properties may be claimed in this application, in applications claiming priority from this application, or in related applications. Such claims, whether directed to a different embodiment or to the same embodiment, and whether broader, narrower, equal, or different in scope in comparison to the original claims, also are regarded as included within the subject matter of this disclosure. [00301] One or more features from any embodiments described herein or in the figures may be combined with one or more features of any other embodiments described herein or in the figures without departing from the scope of this disclosure. [00302] All publications, patents and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Although the foregoing disclosure has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be readily apparent to those of ordinary skill in the art in light of the teachings of this disclosure that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.