Title:
SPLIT LUCIFERASE, AND HIGHLY SENSITIVE VITAMIN D RECEPTOR LIGAND DETECTION METHOD USING SAME
Document Type and Number:
WIPO Patent Application WO/2019/088200
Kind Code:
A1
Abstract:
The present invention pertains to any fusion protein in (1) to (3): (1) a fusion protein containing, in no particular order, the luciferase N-terminal domain (LucN), at least one vitamin D–binding domain of a vitamin D receptor (VDR), and the luciferase C-terminal domain (LucC), and able to additionally include, in no particular order, an LX1X2LL sequence and/or a linker sequence; (2) a fusion protein containing, in no particular order, LucN or LucC, and an LX1X2LL sequence, and able to additionally include, in no particular order, a linker sequence; and (3) a fusion protein containing, in no particular order, at least one vitamin D–binding domain of a VDR, and LucC or LucN, and able to additionally include, in no particular order, a linker sequence. The present invention also pertains to a method for screening, using the fusion protein, for substances which demonstrate the ability to bind to VDRs. The present invention provides a biosensor in which the luminescence increases when an agonist binds thereto, and provides a method for easily screening for substances which bind strongly to vitamin D receptors (VDRs).
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Inventors:
SAKAKI TOSHIYUKI (JP)
NISHIKAWA MIYU (JP)
MANO HIROKI (JP)
NISHIKAWA MIYU (JP)
MANO HIROKI (JP)
Application Number:
PCT/JP2018/040583
Publication Date:
May 09, 2019
Filing Date:
October 31, 2018
Export Citation:
Assignee:
PUBLIC UNIV CORPORATION TOYAMA PREFECTURAL UNIV (JP)
International Classes:
C12N15/62; C07K14/705; C07K19/00; C12N5/10; C12N9/02; C12N15/63; C12Q1/02; C12Q1/66
Foreign References:
| JP2016163559A | 2016-09-08 | |||
| JP2010178676A | 2010-08-19 | |||
| JP2016163559A | 2016-09-08 |
Other References:
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ZELLA L. A. ET AL.: "The vitamin D receptor interacts preferentially with DRIP205-like LxxLL motifs, Arch", BIOCHEM. BIOPHYS., vol. 460, 2007, pages 206 - 212, XP029280400, DOI: doi:10.1016/j.abb.2006.12.016
MANO H. ET AL.: "Novel split luciferase-based biosensors for evaluation of vitamin D receptor ligands and their application to estimate CYP27B1 activity in living cells", J. STEROID BIOCHEM. MOL. BIOL., vol. 183, 9 July 2018 (2018-07-09), pages 221 - 227, XP055612215
MANO H. ET AL.: "Novel biosensor using split-luciferase for detecting vitamin D receptor ligands based on the interaction between vitamin D receptor and coactivator", BIOCHEM. BIOPHYS . RES. COMMUN., vol. 505, 26 September 2018 (2018-09-26), pages 460 - 465, XP055612218
AWAIS M. ET AL.: "A fluorescent indicator to visualize activities of the androgen receptor ligands in single living cells", ANGEW. CHEM. INT. ED., vol. 45, 2006, pages 2707 - 2712, XP055612221
D. ABET. SAKAKIT. KUSUDOA. KITTAKAN. SAITOY. SUHARAT. FUJISHIMAH. TAKAYAMAH. HAMAMOTOM. KAMAKURA: "Metabolism of 2 alpha-propoxy-1 alpha,25-dihydroxyvitamin D3 and 2 alpha-(3-hydroxypropoxy)-1 alpha,25-dihydroxyvitamin D3 by human CYP27A1 and CYP24A1", DRUG METABOLISM AND DISPOSITION: THE BIOLOGICAL FATE OF CHEMICALS, vol. 33, 2005, pages 778 - 784
K. YASUDAS. IKUSHIROM. KAMAKURAM. TAKANON. SAITOA. KITTAKAT.C. CHENM. OHTAT. SAKAKI: "Human cytochrome P450-dependent differential metabolism among three 2alpha-substituted-lalpha,25-dihydroxyvitamin D(3) analogs", THE JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, vol. 133, 2013, pages 84 - 92
M. NAKABAYASHIY. TSUKAHARAY. IWASAKI-MIYAMOTOM. MIHORI-SHIMAZAKIS. YAMADAS. INABAM. ODAM. SHIMIZUM. MAKISHIMAH. TOKIWA: "Crystal structures of hereditary vitamin D-resistant rickets-associated vitamin D receptor mutants R270L and W282R bound to 1,25-dihydroxyvitamin D3 and synthetic ligands", JOURNAL OF MEDICINAL CHEMISTRY, vol. 56, 2013, pages 6745 - 6760
H. MANOM. NISHIKAWAK. YASUDAS. IKUSHIRON. SAITOM. TAKANOA. KITTAKAT. SAKAKI: "Development of Novel Bioluminescent Sensor to Detect and Discriminate between Vitamin D Receptor Agonists and Antagonists in Living Cells", BIOCONJUGATE CHEMISTRY, vol. 26, 2015, pages 2038 - 2045
L.A. ZELLAC.Y. CHANGD.P. MCDONNELLJ.W. PIKE: "The vitamin D receptor interacts preferentially with DRIP205-like LxxLL motifs", ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, vol. 460, 2007, pages 206 - 212
"Firefly Luciferase Enzyme Fragment Complementation for Imaging in Cells and Living Animals", ANAL.CHEM., vol. 77, 2005, pages 1295 - 1302
NLUC.M.P. HALLJ. UNCHB.F. BINKOWSKIM.P. VALLEYB.L. BUTLERM.G. WOODP. OTTOK. ZIMMERMANG. VIDUGIRIS: "Engineered luciferase reporter from a deep sea shrimp utilizing a novel imidazopyrazinone substrate", ACS CHEM BIOL, vol. 7, 2012, pages 1848 - 1857, XP055256124, DOI: 10.1021/cb3002478
S. INOUYEK. WATANABEH. NAKAMURAO. SHIMOMURA: "Secretional luciferase of the luminous shrimp Oplophorus gracilirostris: cDNA cloning of a novel imidazopyrazinone luciferase (1", FEBS LETT, vol. 481, 2000, pages 19 - 25, XP004337549, DOI: 10.1016/S0014-5793(00)01963-3
C. RACHEZM. GAMBLEC.P. CHANGG.B. ATKINSM.A. LAZARL.P. FREEDMAN: "The DRIP complex and SRC-l/pl60 coactivators share similar nuclear receptor binding determinants but constitute functionally distinct complexes", MOL CELL BIOL, vol. 20, 2000, pages 2718 - 2726
C. CHANGJ.D. NORRISH. GRONL.A. PAIGEP.T. HAMILTOND.J. KENAND. FOWLKESD.P. MCDONNELL: "Dissection of the LXXLL nuclear receptor-coactivator interaction motif using combinatorial peptide libraries: discovery of peptide antagonists of estrogen receptors alpha and beta", MOL CELL BIOL, vol. 19, 1999, pages 8226 - 8239, XP001120691
B. HEE.M. WILSON: "Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs", MOL CELL BIOL, vol. 23, 2003, pages 2135 - 2150
G. LIZ. HUANGC. ZHANGB. J. DONGR. H. GUOH. W. YUEL. T. YANX. H. XING: "Construction of a linker library with widely controllable flexibility for fusion protein design", APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, vol. 100, 2016, pages 215 - 225
"The Unique Tryptophan Residue of the Vitamin D Receptor Is Critical for Ligand Binding and Transcriptional Activation", JOURNAL OF BONE AND MINERAL RESEARCH, vol. 16, no. 1, 2001, pages 39 - 45
"Novel Compound Heterozygous Mutations in the Vitamin D Receptor Gene in a Korean Girl with Hereditary Vitamin D Resistant Rickets", J KOREAN MED SCI, vol. 26, 2011, pages 1111 - 1114
"Crystal Structures of Hereditary Vitamin D-Resistant Rickets-Associated Vitamin D Receptor Mutants R270L and W282R Bound to 1,25-Dihydroxyvitamin D3 and Synthetic Ligands", J. MED.CHEM., vol. 56, 2013, pages 6745 - 6760
"Mutations in the vitamin D receptor and hereditary vitamin D-resistant rickets", BONEKEY REPORTS, vol. 3, no. 510, 2014, pages 1 - 11
"Crystal structure of hereditary vitamin D-resistant rickets-Associated mutant H305Q of vitamin D nuclear receptor bound to its natural ligand", JOURNAL OF STEROID BIOCHEMISTRY & MOLECULAR BIOLOGY, vol. 121, 2010, pages 84 - 87
"Mutations in the Vitamin D Receptor Gene in Four Patients with Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets", ARQ BRAS ENDOCRINOL METAB, vol. 52/8, 2008, pages 1244 - 1251
"The Vitamin D Receptor and the Syndrome of Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets", ENDOCRINE REVIEWS, vol. 20, no. 2, 1999, pages 156 - 188
N. ROCHELJ.M. WURTZA. MITSCHLERB. KLAHOLZD. MORAS: "The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand", MOLECULAR CELL, vol. 5, 2000, pages 173 - 179
ZELLA L. A. ET AL.: "The vitamin D receptor interacts preferentially with DRIP205-like LxxLL motifs, Arch", BIOCHEM. BIOPHYS., vol. 460, 2007, pages 206 - 212, XP029280400, DOI: doi:10.1016/j.abb.2006.12.016
MANO H. ET AL.: "Novel split luciferase-based biosensors for evaluation of vitamin D receptor ligands and their application to estimate CYP27B1 activity in living cells", J. STEROID BIOCHEM. MOL. BIOL., vol. 183, 9 July 2018 (2018-07-09), pages 221 - 227, XP055612215
MANO H. ET AL.: "Novel biosensor using split-luciferase for detecting vitamin D receptor ligands based on the interaction between vitamin D receptor and coactivator", BIOCHEM. BIOPHYS . RES. COMMUN., vol. 505, 26 September 2018 (2018-09-26), pages 460 - 465, XP055612218
AWAIS M. ET AL.: "A fluorescent indicator to visualize activities of the androgen receptor ligands in single living cells", ANGEW. CHEM. INT. ED., vol. 45, 2006, pages 2707 - 2712, XP055612221
D. ABET. SAKAKIT. KUSUDOA. KITTAKAN. SAITOY. SUHARAT. FUJISHIMAH. TAKAYAMAH. HAMAMOTOM. KAMAKURA: "Metabolism of 2 alpha-propoxy-1 alpha,25-dihydroxyvitamin D3 and 2 alpha-(3-hydroxypropoxy)-1 alpha,25-dihydroxyvitamin D3 by human CYP27A1 and CYP24A1", DRUG METABOLISM AND DISPOSITION: THE BIOLOGICAL FATE OF CHEMICALS, vol. 33, 2005, pages 778 - 784
K. YASUDAS. IKUSHIROM. KAMAKURAM. TAKANON. SAITOA. KITTAKAT.C. CHENM. OHTAT. SAKAKI: "Human cytochrome P450-dependent differential metabolism among three 2alpha-substituted-lalpha,25-dihydroxyvitamin D(3) analogs", THE JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, vol. 133, 2013, pages 84 - 92
M. NAKABAYASHIY. TSUKAHARAY. IWASAKI-MIYAMOTOM. MIHORI-SHIMAZAKIS. YAMADAS. INABAM. ODAM. SHIMIZUM. MAKISHIMAH. TOKIWA: "Crystal structures of hereditary vitamin D-resistant rickets-associated vitamin D receptor mutants R270L and W282R bound to 1,25-dihydroxyvitamin D3 and synthetic ligands", JOURNAL OF MEDICINAL CHEMISTRY, vol. 56, 2013, pages 6745 - 6760
H. MANOM. NISHIKAWAK. YASUDAS. IKUSHIRON. SAITOM. TAKANOA. KITTAKAT. SAKAKI: "Development of Novel Bioluminescent Sensor to Detect and Discriminate between Vitamin D Receptor Agonists and Antagonists in Living Cells", BIOCONJUGATE CHEMISTRY, vol. 26, 2015, pages 2038 - 2045
L.A. ZELLAC.Y. CHANGD.P. MCDONNELLJ.W. PIKE: "The vitamin D receptor interacts preferentially with DRIP205-like LxxLL motifs", ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, vol. 460, 2007, pages 206 - 212
"Firefly Luciferase Enzyme Fragment Complementation for Imaging in Cells and Living Animals", ANAL.CHEM., vol. 77, 2005, pages 1295 - 1302
NLUC.M.P. HALLJ. UNCHB.F. BINKOWSKIM.P. VALLEYB.L. BUTLERM.G. WOODP. OTTOK. ZIMMERMANG. VIDUGIRIS: "Engineered luciferase reporter from a deep sea shrimp utilizing a novel imidazopyrazinone substrate", ACS CHEM BIOL, vol. 7, 2012, pages 1848 - 1857, XP055256124, DOI: 10.1021/cb3002478
S. INOUYEK. WATANABEH. NAKAMURAO. SHIMOMURA: "Secretional luciferase of the luminous shrimp Oplophorus gracilirostris: cDNA cloning of a novel imidazopyrazinone luciferase (1", FEBS LETT, vol. 481, 2000, pages 19 - 25, XP004337549, DOI: 10.1016/S0014-5793(00)01963-3
C. RACHEZM. GAMBLEC.P. CHANGG.B. ATKINSM.A. LAZARL.P. FREEDMAN: "The DRIP complex and SRC-l/pl60 coactivators share similar nuclear receptor binding determinants but constitute functionally distinct complexes", MOL CELL BIOL, vol. 20, 2000, pages 2718 - 2726
C. CHANGJ.D. NORRISH. GRONL.A. PAIGEP.T. HAMILTOND.J. KENAND. FOWLKESD.P. MCDONNELL: "Dissection of the LXXLL nuclear receptor-coactivator interaction motif using combinatorial peptide libraries: discovery of peptide antagonists of estrogen receptors alpha and beta", MOL CELL BIOL, vol. 19, 1999, pages 8226 - 8239, XP001120691
B. HEE.M. WILSON: "Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs", MOL CELL BIOL, vol. 23, 2003, pages 2135 - 2150
G. LIZ. HUANGC. ZHANGB. J. DONGR. H. GUOH. W. YUEL. T. YANX. H. XING: "Construction of a linker library with widely controllable flexibility for fusion protein design", APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, vol. 100, 2016, pages 215 - 225
"The Unique Tryptophan Residue of the Vitamin D Receptor Is Critical for Ligand Binding and Transcriptional Activation", JOURNAL OF BONE AND MINERAL RESEARCH, vol. 16, no. 1, 2001, pages 39 - 45
"Novel Compound Heterozygous Mutations in the Vitamin D Receptor Gene in a Korean Girl with Hereditary Vitamin D Resistant Rickets", J KOREAN MED SCI, vol. 26, 2011, pages 1111 - 1114
"Crystal Structures of Hereditary Vitamin D-Resistant Rickets-Associated Vitamin D Receptor Mutants R270L and W282R Bound to 1,25-Dihydroxyvitamin D3 and Synthetic Ligands", J. MED.CHEM., vol. 56, 2013, pages 6745 - 6760
"Mutations in the vitamin D receptor and hereditary vitamin D-resistant rickets", BONEKEY REPORTS, vol. 3, no. 510, 2014, pages 1 - 11
"Crystal structure of hereditary vitamin D-resistant rickets-Associated mutant H305Q of vitamin D nuclear receptor bound to its natural ligand", JOURNAL OF STEROID BIOCHEMISTRY & MOLECULAR BIOLOGY, vol. 121, 2010, pages 84 - 87
"Mutations in the Vitamin D Receptor Gene in Four Patients with Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets", ARQ BRAS ENDOCRINOL METAB, vol. 52/8, 2008, pages 1244 - 1251
"The Vitamin D Receptor and the Syndrome of Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets", ENDOCRINE REVIEWS, vol. 20, no. 2, 1999, pages 156 - 188
N. ROCHELJ.M. WURTZA. MITSCHLERB. KLAHOLZD. MORAS: "The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand", MOLECULAR CELL, vol. 5, 2000, pages 173 - 179
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SIKS & CO. (JP)
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