Title:
MODIFICATION OF TRNA T-STEM FOR ENHANCING N-METHYL AMINO ACID INCORPORATION
Document Type and Number:
WIPO Patent Application WO/2021/100833
Kind Code:
A1
Abstract:
The present invention addresses the problem of developing a method for synthesizing a novel peptide which can co-incorporate a plurality of different N-methyl amino acids and discover a highly N-methylated peptide having improved membrane-permeability and stability to proteolysis. The present invention provides tRNA that encodes N-methyl amino acids and has a T-stem in which N1N2GGN3 pairs with N4CCN5U (N1 is G or A, one among N2 and N4 is G and the other is C, and N3 and N4 are any pairing amino acids).
Inventors:
SUGA HIROAKI (JP)
KATOH TAKAYUKI (JP)
IWANE YOSHIHIKO (JP)
KATOH TAKAYUKI (JP)
IWANE YOSHIHIKO (JP)
Application Number:
PCT/JP2020/043289
Publication Date:
May 27, 2021
Filing Date:
November 19, 2020
Export Citation:
Assignee:
UNIV TOKYO (JP)
International Classes:
C07K1/00; C07K7/00; C12M1/00; C12N15/11; C12P21/02; C40B40/08; C40B40/10
Domestic Patent References:
| WO2012033154A1 | 2012-03-15 | |||
| WO2019077887A1 | 2019-04-25 | |||
| WO2015030014A1 | 2015-03-05 | |||
| WO2008117833A1 | 2008-10-02 | |||
| WO2012074129A1 | 2012-06-07 |
Other References:
KATOH, T. ET AL.: "Logical engineering of D-arm and T-stem of tRNA that enhances D-amino acid incorporation", NUCLEIC ACIDS RESEARCH, vol. 45, no. 22, 2017, pages 12601 - 12610, XP055598170, DOI: 10.1093/nar/gkx1129
KATOH, T. ET AL.: "Ribosomal Incorporation of Consecutive beta-Amino Acids", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 140, no. 38, 17 September 2018 (2018-09-17), pages 12159 - 12167, XP055825755
PASSIOURA, T.KATOH, T.GOTO, Y.SUGA, H.: "Selection-based discovery of druglike macrocyclic peptides", ANNU. REV. BIOCHEM., vol. 83, 2014, pages 727 - 752, XP055561850, DOI: 10.1146/annurev-biochem-060713-035456
DRIGGERS, E. M.HALE, S. PLEE, J.TERRETT, N. K.: "The exploration of macrocycles for drug discovery-an underexploited structural class", NAT. REV. DRUG DISCOV., vol. 7, 2008, pages 608 - 624, XP055151640, DOI: 10.1038/nrd2590
KOEHN, F. E.CARTER, G. T.: "The evolving role of natural products in drug discovery", NAT. REV. DRUG DISCOV., vol. 4, 2005, pages 206 - 220
HANDSCHUMACHER, R. E.HARDING, M. W.RICE, J.DRUGGE, R. J.SPEICHER, D. W.: "Cyclophilin: a specific cytosolic binding protein for cyclosporin A", SCIENCE, vol. 226, 1984, pages 544 - 547
TAKAHASHI, N.HAYANO, T.SUZUKI, M.: "Peptidyl-Prolyl Cis-Trans Isomerase Is the Cyclosporin-a-Binding Protein Cyclophilin", NATURE, vol. 337, 1989, pages 473 - 475, XP000082642, DOI: 10.1038/337473a0
WALSH, C. T.ZYDOWSKY, L. D.MCKEON, F. D.: "Cyclosporin A, the cyclophilin class of peptidylprolyl isomerases, and blockade of T cell signal transduction", J. BIOL. CHEM., vol. 267, 1992, pages 13115 - 13118
ALTSCHUH, D.VIX, O.REES, B.THIERRY, J. C.: "A conformation of cyclosporin A in aqueous environment revealed by the X-ray structure of a cyclosporin-Fab complex", SCIENCE, vol. 256, 1992, pages 92 - 94
CONRADI, R. A.HILGERS, A. R.HO, N. F.BURTON, P. S.: "The influence of peptide structure on transport across Caco-2 cells. II. Peptide bond modification which results in improved permeability", PHARM. RES., vol. 9, 1992, pages 435 - 439, XP000607192, DOI: 10.1023/A:1015867608405
HAVIV, F. ET AL.: "Effect of N-methyl substitution of the peptide bonds in luteinizing hormone-releasing hormone agonists", J. MED. CHEM., vol. 36, 1993, pages 363 - 369
CHIKHALE, E. G.NG, K. Y.BURTON, P. S.BORCHARDT, R. T.: "Hydrogen bonding potential as a determinant of the in vitro and in situ blood-brain barrier permeability of peptides", PHARM. RES., vol. 11, 1994, pages 412 - 419
MILLER, S. M. ET AL.: "Comparison of the Proteolytic Susceptibilities of Homologous L-Amino-Acid, D-Amino-Acid, and N-Substituted Glycine Peptide and Peptoid Oligomers", DRUG DEV. RES., vol. 35, 1995, pages 20 - 32
ROBERTS, R. W.SZOSTAK, J. W.: "RNA-peptide fusions for the in vitro selection of peptides and proteins", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 94, 1997, pages 12297 - 12302, XP002913434, DOI: 10.1073/pnas.94.23.12297
MURAKAMI, H.OHTA, A.ASHIGAI, H.SUGA, H.: "A highly flexible tRNA acylation method for non-natural polypeptide synthesis", NAT. METHODS, vol. 3, 2006, pages 357 - 359, XP003013897, DOI: 10.1038/nmeth877
OHTA, A.MURAKAMI, H.HIGASHIMURA, E.SUGA, H.: "Synthesis of polyester by means of genetic code reprogramming", CHEM. BIOL., vol. 14, 2007, pages 1315 - 1322, XP022392655
GOTO, Y. ET AL.: "Reprogramming the translation initiation for the synthesis of physiologically stable cyclic peptides", ACS CHEMICAL BIOLOGY, vol. 3, 2008, pages 120 - 129, XP002564832, DOI: 10.1021/cb700233t
GOTO, Y.MURAKAMI, H.SUGA, H.: "Initiating translation with D-amino acids", RNA, vol. 14, 2008, pages 1390 - 1398, XP002564831, DOI: 10.1261/RNA.1020708
H. F. KUNG ET AL., THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 252, no. 19, 1977, pages 6889 - 6894
M. C. GONZA ET AL., PROCEEDING OF NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 82, 1985, pages 1648 - 1652
M. Y. PAVLOVM. EHRENBERG, ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, vol. 328, no. 1, 1996, pages 9 - 16
Y. SHIMIZU ET AL., NATURE BIOTECHNOLOGY, vol. 19, no. 8, 2001, pages 751 - 755
H. OHASHI ET AL., BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 352, no. 1, 2007, pages 270 - 276
KAWAKAMI, T. ET AL., NATURE CHEMICAL BIOLOGY, vol. 5, 2009, pages 888 - 890
YAMAGISHI, Y. ET AL., CHEMBIOCHEM, vol. 10, 2009, pages 1469 - 1472
SAKO, Y. ET AL., JOURNAL OF AMERICAN CHEMICAL SOCIETY, vol. 130, 2008, pages 7932 - 7934
GOTO, Y. ET AL., ACS CHEMICAL BIOLOGY, vol. 3, 2008, pages 120 - 129
KAWAKAMI T. ET AL., CHEMISTRY & BIOLOGY, vol. 15, 2008, pages 32 - 42
NISSEN, P. ET AL.: "Crystal structure of the ternary complex of Phe-tRNAPhe, EF-Tu, and a GTP analog", SCIENCE, vol. 270, 1995, pages 1464 - 1472, XP055014172
GOTO, Y.KATOH, T.SUGA, H.: "Flexizymes for genetic code reprogramming", NAT PROTOC, vol. 6, 2011, pages 779 - 790, XP009158277, DOI: 10.1038/nprot.2011.331
KAWAKAMI, T.MURAKAMI, H.SUGA, H.: "Messenger RNA-programmed incorporation of multiple N-methyl amino acids into linear and cyclic peptides", CHEM. BIOL., vol. 15, 2008, pages 32 - 42, XP022428215, DOI: 10.1016/j.chembiol.2007.12.008
SHIMIZU, Y. ET AL.: "Cell-free translation reconstituted with purified components", NAT. BIOTECHNOL., vol. 19, 2001, pages 751 - 755, XP037163597, DOI: 10.1038/90802
LARIVIERE, F. J.WOLFSON, A. D.UHLENBECK, O. C.: "Uniform binding of aminoacyl-tRNAs to elongation factor Tu by thermodynamic compensation", SCIENCE, vol. 294, 2001, pages 165 - 168
YAMAGISHI, Y. ET AL.: "Natural product-like macrocyclic N-methyl-peptide inhibitors against a ubiquitin ligase uncovered from a ribosome-expressed de novo library", CHEM. BIOL., vol. 18, 2011, pages 1562 - 1570, XP028348893, DOI: 10.1016/j.chembiol.2011.09.013
SCHRADER, J. M.CHAPMAN, S. J.UHLENBECK, O. C.: "Understanding the sequence specificity of tRNA binding to elongation factor Tu using tRNA mutagenesis", J. MOL. BIOL., vol. 386, 2009, pages 1255 - 1264, XP025996414, DOI: 10.1016/j.jmb.2009.01.021
SCHRADER, J. M.CHAPMAN, S. J.UHLENBECK, O. C.: "Tuning the affinity of aminoacyl-tRNA to elongation factor Tu for optimal decoding", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 108, 2011, pages 5215 - 5220
MITTELSTAET, J.KONEVEGA, A. L.RODNINA, M. V.: "A kinetic safety gate controlling the delivery of unnatural amino acids to the ribosome", J. AM. CHEM. SOC., vol. 135, 2013, pages 17031 - 17038
SUBTELNY, A. O.HARTMAN, M. C.SZOSTAK, J. W.: "Ribosomal synthesis of N-methyl peptides", J. AM. CHEM. SOC., vol. 130, 2008, pages 6131 - 6136, XP055376645, DOI: 10.1021/ja710016v
OHTSUKI, T.MANABE, T.SISIDO, M.: "Multiple incorporation of non-natural amino acids into a single protein using tRNAs with non-standard structures", FEBS LETT, vol. 579, 2005, pages 6769 - 6774, XP005205440, DOI: 10.1016/j.febslet.2005.11.010
IWANE, Y. ET AL.: "Expanding the amino acid repertoire of ribosomal polypeptide synthesis via the artificial division of codon boxes", NAT CHEM, vol. 8, 2016, pages 317 - 325, XP055508589, DOI: 10.1038/nchem.2446
See also references of EP 4063377A1
KATOH, T. ET AL.: "Ribosomal Incorporation of Consecutive beta-Amino Acids", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 140, no. 38, 17 September 2018 (2018-09-17), pages 12159 - 12167, XP055825755
PASSIOURA, T.KATOH, T.GOTO, Y.SUGA, H.: "Selection-based discovery of druglike macrocyclic peptides", ANNU. REV. BIOCHEM., vol. 83, 2014, pages 727 - 752, XP055561850, DOI: 10.1146/annurev-biochem-060713-035456
DRIGGERS, E. M.HALE, S. PLEE, J.TERRETT, N. K.: "The exploration of macrocycles for drug discovery-an underexploited structural class", NAT. REV. DRUG DISCOV., vol. 7, 2008, pages 608 - 624, XP055151640, DOI: 10.1038/nrd2590
KOEHN, F. E.CARTER, G. T.: "The evolving role of natural products in drug discovery", NAT. REV. DRUG DISCOV., vol. 4, 2005, pages 206 - 220
HANDSCHUMACHER, R. E.HARDING, M. W.RICE, J.DRUGGE, R. J.SPEICHER, D. W.: "Cyclophilin: a specific cytosolic binding protein for cyclosporin A", SCIENCE, vol. 226, 1984, pages 544 - 547
TAKAHASHI, N.HAYANO, T.SUZUKI, M.: "Peptidyl-Prolyl Cis-Trans Isomerase Is the Cyclosporin-a-Binding Protein Cyclophilin", NATURE, vol. 337, 1989, pages 473 - 475, XP000082642, DOI: 10.1038/337473a0
WALSH, C. T.ZYDOWSKY, L. D.MCKEON, F. D.: "Cyclosporin A, the cyclophilin class of peptidylprolyl isomerases, and blockade of T cell signal transduction", J. BIOL. CHEM., vol. 267, 1992, pages 13115 - 13118
ALTSCHUH, D.VIX, O.REES, B.THIERRY, J. C.: "A conformation of cyclosporin A in aqueous environment revealed by the X-ray structure of a cyclosporin-Fab complex", SCIENCE, vol. 256, 1992, pages 92 - 94
CONRADI, R. A.HILGERS, A. R.HO, N. F.BURTON, P. S.: "The influence of peptide structure on transport across Caco-2 cells. II. Peptide bond modification which results in improved permeability", PHARM. RES., vol. 9, 1992, pages 435 - 439, XP000607192, DOI: 10.1023/A:1015867608405
HAVIV, F. ET AL.: "Effect of N-methyl substitution of the peptide bonds in luteinizing hormone-releasing hormone agonists", J. MED. CHEM., vol. 36, 1993, pages 363 - 369
CHIKHALE, E. G.NG, K. Y.BURTON, P. S.BORCHARDT, R. T.: "Hydrogen bonding potential as a determinant of the in vitro and in situ blood-brain barrier permeability of peptides", PHARM. RES., vol. 11, 1994, pages 412 - 419
MILLER, S. M. ET AL.: "Comparison of the Proteolytic Susceptibilities of Homologous L-Amino-Acid, D-Amino-Acid, and N-Substituted Glycine Peptide and Peptoid Oligomers", DRUG DEV. RES., vol. 35, 1995, pages 20 - 32
ROBERTS, R. W.SZOSTAK, J. W.: "RNA-peptide fusions for the in vitro selection of peptides and proteins", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 94, 1997, pages 12297 - 12302, XP002913434, DOI: 10.1073/pnas.94.23.12297
MURAKAMI, H.OHTA, A.ASHIGAI, H.SUGA, H.: "A highly flexible tRNA acylation method for non-natural polypeptide synthesis", NAT. METHODS, vol. 3, 2006, pages 357 - 359, XP003013897, DOI: 10.1038/nmeth877
OHTA, A.MURAKAMI, H.HIGASHIMURA, E.SUGA, H.: "Synthesis of polyester by means of genetic code reprogramming", CHEM. BIOL., vol. 14, 2007, pages 1315 - 1322, XP022392655
GOTO, Y. ET AL.: "Reprogramming the translation initiation for the synthesis of physiologically stable cyclic peptides", ACS CHEMICAL BIOLOGY, vol. 3, 2008, pages 120 - 129, XP002564832, DOI: 10.1021/cb700233t
GOTO, Y.MURAKAMI, H.SUGA, H.: "Initiating translation with D-amino acids", RNA, vol. 14, 2008, pages 1390 - 1398, XP002564831, DOI: 10.1261/RNA.1020708
H. F. KUNG ET AL., THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 252, no. 19, 1977, pages 6889 - 6894
M. C. GONZA ET AL., PROCEEDING OF NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 82, 1985, pages 1648 - 1652
M. Y. PAVLOVM. EHRENBERG, ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, vol. 328, no. 1, 1996, pages 9 - 16
Y. SHIMIZU ET AL., NATURE BIOTECHNOLOGY, vol. 19, no. 8, 2001, pages 751 - 755
H. OHASHI ET AL., BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 352, no. 1, 2007, pages 270 - 276
KAWAKAMI, T. ET AL., NATURE CHEMICAL BIOLOGY, vol. 5, 2009, pages 888 - 890
YAMAGISHI, Y. ET AL., CHEMBIOCHEM, vol. 10, 2009, pages 1469 - 1472
SAKO, Y. ET AL., JOURNAL OF AMERICAN CHEMICAL SOCIETY, vol. 130, 2008, pages 7932 - 7934
GOTO, Y. ET AL., ACS CHEMICAL BIOLOGY, vol. 3, 2008, pages 120 - 129
KAWAKAMI T. ET AL., CHEMISTRY & BIOLOGY, vol. 15, 2008, pages 32 - 42
NISSEN, P. ET AL.: "Crystal structure of the ternary complex of Phe-tRNAPhe, EF-Tu, and a GTP analog", SCIENCE, vol. 270, 1995, pages 1464 - 1472, XP055014172
GOTO, Y.KATOH, T.SUGA, H.: "Flexizymes for genetic code reprogramming", NAT PROTOC, vol. 6, 2011, pages 779 - 790, XP009158277, DOI: 10.1038/nprot.2011.331
KAWAKAMI, T.MURAKAMI, H.SUGA, H.: "Messenger RNA-programmed incorporation of multiple N-methyl amino acids into linear and cyclic peptides", CHEM. BIOL., vol. 15, 2008, pages 32 - 42, XP022428215, DOI: 10.1016/j.chembiol.2007.12.008
SHIMIZU, Y. ET AL.: "Cell-free translation reconstituted with purified components", NAT. BIOTECHNOL., vol. 19, 2001, pages 751 - 755, XP037163597, DOI: 10.1038/90802
LARIVIERE, F. J.WOLFSON, A. D.UHLENBECK, O. C.: "Uniform binding of aminoacyl-tRNAs to elongation factor Tu by thermodynamic compensation", SCIENCE, vol. 294, 2001, pages 165 - 168
YAMAGISHI, Y. ET AL.: "Natural product-like macrocyclic N-methyl-peptide inhibitors against a ubiquitin ligase uncovered from a ribosome-expressed de novo library", CHEM. BIOL., vol. 18, 2011, pages 1562 - 1570, XP028348893, DOI: 10.1016/j.chembiol.2011.09.013
SCHRADER, J. M.CHAPMAN, S. J.UHLENBECK, O. C.: "Understanding the sequence specificity of tRNA binding to elongation factor Tu using tRNA mutagenesis", J. MOL. BIOL., vol. 386, 2009, pages 1255 - 1264, XP025996414, DOI: 10.1016/j.jmb.2009.01.021
SCHRADER, J. M.CHAPMAN, S. J.UHLENBECK, O. C.: "Tuning the affinity of aminoacyl-tRNA to elongation factor Tu for optimal decoding", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 108, 2011, pages 5215 - 5220
MITTELSTAET, J.KONEVEGA, A. L.RODNINA, M. V.: "A kinetic safety gate controlling the delivery of unnatural amino acids to the ribosome", J. AM. CHEM. SOC., vol. 135, 2013, pages 17031 - 17038
SUBTELNY, A. O.HARTMAN, M. C.SZOSTAK, J. W.: "Ribosomal synthesis of N-methyl peptides", J. AM. CHEM. SOC., vol. 130, 2008, pages 6131 - 6136, XP055376645, DOI: 10.1021/ja710016v
OHTSUKI, T.MANABE, T.SISIDO, M.: "Multiple incorporation of non-natural amino acids into a single protein using tRNAs with non-standard structures", FEBS LETT, vol. 579, 2005, pages 6769 - 6774, XP005205440, DOI: 10.1016/j.febslet.2005.11.010
IWANE, Y. ET AL.: "Expanding the amino acid repertoire of ribosomal polypeptide synthesis via the artificial division of codon boxes", NAT CHEM, vol. 8, 2016, pages 317 - 325, XP055508589, DOI: 10.1038/nchem.2446
See also references of EP 4063377A1
Attorney, Agent or Firm:
INABA, Yoshiyuki et al. (JP)
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