WO2002064632A3 - Crystallized ppar$g(a) ligand binding domain polypeptide and screening methods employing same - Google Patents

Crystallized ppar$g(a) ligand binding domain polypeptide and screening methods employing same Download PDF

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Publication number
WO2002064632A3
WO2002064632A3 PCT/US2002/003278 US0203278W WO02064632A3 WO 2002064632 A3 WO2002064632 A3 WO 2002064632A3 US 0203278 W US0203278 W US 0203278W WO 02064632 A3 WO02064632 A3 WO 02064632A3
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WO
WIPO (PCT)
Prior art keywords
binding domain
ligand binding
ppar
domain polypeptide
crystallized
Prior art date
Application number
PCT/US2002/003278
Other languages
French (fr)
Other versions
WO2002064632A2 (en
Inventor
Millard Hurst Lambert Iii
Valerie Gail Montana
Huaqiang Eric Xu
Original Assignee
Smithkline Beecham Corp
Millard Hurst Lambert Iii
Valerie Gail Montana
Huaqiang Eric Xu
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Smithkline Beecham Corp, Millard Hurst Lambert Iii, Valerie Gail Montana, Huaqiang Eric Xu filed Critical Smithkline Beecham Corp
Priority to US10/467,048 priority Critical patent/US20040137518A1/en
Publication of WO2002064632A2 publication Critical patent/WO2002064632A2/en
Publication of WO2002064632A3 publication Critical patent/WO2002064632A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70571—Receptors; Cell surface antigens; Cell surface determinants for neuromediators, e.g. serotonin receptor, dopamine receptor
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2299/00—Coordinates from 3D structures of peptides, e.g. proteins or enzymes

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Cell Biology (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Peptides Or Proteins (AREA)

Abstract

A solved three-dimensional crystal structure of a PPARα ligand binding domain polypeptide is disclosed, along with a crystal form of the PPARα ligand binding domain polypeptide. Methods of designing modulators of the biological activity of PPARα and other PPAR ligand binding domain polypeptides are also disclosed.
PCT/US2002/003278 2001-02-01 2002-01-31 Crystallized ppar$g(a) ligand binding domain polypeptide and screening methods employing same WO2002064632A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US10/467,048 US20040137518A1 (en) 2002-01-31 2002-01-31 CRYSTALLIZED PPARa LIGAND BINDING DOMAIN POLYPEPTIDE AND SCREENING METHODS EMPLOYING SAME

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US26569801P 2001-02-01 2001-02-01
US60/265,698 2001-02-01

Publications (2)

Publication Number Publication Date
WO2002064632A2 WO2002064632A2 (en) 2002-08-22
WO2002064632A3 true WO2002064632A3 (en) 2003-08-14

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/003278 WO2002064632A2 (en) 2001-02-01 2002-01-31 Crystallized ppar$g(a) ligand binding domain polypeptide and screening methods employing same

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WO (1) WO2002064632A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004006662A1 (en) * 2002-07-15 2004-01-22 Takeda Pharmaceutical Company Limited DISEASE MODEL ANIMAL CARRYING FOREIGN PPARα GENE TRANSFERRED THEREINTO AND USE THEREOF
FR2861745A1 (en) * 2003-10-31 2005-05-06 Centre Nat Rech Scient Selecting compounds that inhibit the mycobacterial EthR repressor, useful in treatment of tuberculosis and leprosy, improve efficiency of conversion of ethionamide to its active form
US20080286260A1 (en) * 2004-03-26 2008-11-20 Bayer Healthcare Ag Diagnostic and Therapeutics for Diseases Associated with Peroxisome Proliferative Activated Receptor Alpha (Ppara)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000064888A1 (en) * 1999-04-28 2000-11-02 Aventis Pharma Deutschland Gmbh Di-aryl acid derivatives as ppar receptor ligands
WO2000064876A1 (en) * 1999-04-28 2000-11-02 Aventis Pharma Deutschland Gmbh Tri-aryl acid derivatives as ppar receptor ligands

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000064888A1 (en) * 1999-04-28 2000-11-02 Aventis Pharma Deutschland Gmbh Di-aryl acid derivatives as ppar receptor ligands
WO2000064876A1 (en) * 1999-04-28 2000-11-02 Aventis Pharma Deutschland Gmbh Tri-aryl acid derivatives as ppar receptor ligands

Non-Patent Citations (15)

* Cited by examiner, † Cited by third party
Title
CRONET PHILIPPE ET AL: "Structure of the PPARalpha and -gamma ligand binding domain in complex with AZ 242;ligand selectivity and agonist activation in the PPAR family.", STRUCTURE (CAMBRIDGE), vol. 9, no. 8, August 2001 (2001-08-01), August, 2001, pages 699 - 706, XP002221832, ISSN: 0969-2126 *
DATABASE PDB [online] National Institutues of Health (NIH), U.S.A.; 10 December 2001 (2001-12-10), XU ET AL: "Crystal structure of the human PPAR-alpha Ligand-binding domain in complex with an antagonist GW6471 and a SMRT", XP002221837, Database accession no. 1kkq *
DATABASE PDB [online] National Institutues of Health (NIH), U.S.A.; 19 October 2001 (2001-10-19), XU ET AL: "The 2.5 Angstrom resolution crystal structure of the human PPARalpha ligand binding domain with GW409544 and a co-activator peptide", XP002221839, Database accession no. 1k7l *
DATABASE PDB [online] National Institutues of Health (NIH), U.S.A.; 9 March 2001 (2001-03-09), PETERSEN AT AL: "Crystal structure of the ligand-binding domain from the human PPAR-alpha in complex with the agonist AZ 242", XP002221838, Database accession no. 1i7g *
GEARING K L ET AL: "Structure of the mouse peroxisome proliferator activated receptor alpha gene.", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 199, no. 1, 1994, pages 255 - 263, XP002913663, ISSN: 0006-291X *
GIEGE R ET AL: "Crystallogenesis of biological macromolecules. Biological, microgravity and other physicochemical aspects", PROGRESS IN CRYSTAL GROWTH AND CHARACTERIZATION OF MATERIALS, ELSEVIER PUBLISHING, BARKING, GB, vol. 30, no. 4, 1995, pages 237 - 281, XP004048541, ISSN: 0960-8974 *
GILLILAND G L ET AL: "Crystallization of biological macromolecules for X-ray diffraction studies", CURRENT OPINION IN STRUCTURAL BIOLOGY, CURRENT BIOLOGY LTD., LONDON, GB, vol. 6, no. 5, October 1996 (1996-10-01), pages 595 - 603, XP002128062, ISSN: 0959-440X *
KLIEWER S A ET AL: "Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. UNITED STATES 29 APR 1997, vol. 94, no. 9, 29 April 1997 (1997-04-29), pages 4318 - 4323, XP002229916, ISSN: 0027-8424 *
LEWIS D F V ET AL: "Molecular modelling of the rat peroxisome proliferator-activated receptor -alpha (rPPARalpha) by homology with the human retinoic acid X receptor alpha (hRXRalpha) and investigation of ligand binding interactions I: QSARs.", TOXICOLOGY IN VITRO, vol. 12, no. 6, December 1998 (1998-12-01), pages 619 - 632, XP002221833, ISSN: 0887-2333 *
LUFT J R ET AL: "EXPERIENCES WITH HANGMAN: A MACROMOLECULAR HANGING DROP VAPOR DIFUSION TECHNIQUE", JOURNAL OF CRYSTAL GROWTH, NORTH-HOLLAND PUBLISHING CO. AMSTERDAM, NL, vol. 122, no. 1 / 4, 2 August 1992 (1992-08-02), pages 181 - 185, XP000306493, ISSN: 0022-0248 *
MCPHERSON A ET AL: "THE SCIENCE OF MACROMOLECULAR CRYSTALLIZATION", STRUCTURE, CURRENT BIOLOGY LTD., PHILADELPHIA, PA, US, vol. 3, 1995, pages 759 - 768, XP001013101, ISSN: 0969-2126 *
SAKAMOTO J ET AL: "Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone.", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. UNITED STATES 30 NOV 2000, vol. 278, no. 3, 30 November 2000 (2000-11-30), pages 704 - 711, XP002229915, ISSN: 0006-291X *
SHER T ET AL: "CDNA CLONING, CHROMOSOMAL MAPPING, AND FUNCTIONAL CHARACTERIZATION OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, PA, US, vol. 32, no. 21, 1993, pages 5598 - 5604, XP000577090, ISSN: 0006-2960 *
XU H E ET AL: "STRUCTURAL DETERMINANTS OF LIGAND BINDING SELECTIVITY BETWEEN THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 98, no. 24, 20 November 2001 (2001-11-20), pages 13919 - 13924, XP001066308, ISSN: 0027-8424 *
XU H ERIC ET AL: "Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha.", NATURE (LONDON), vol. 415, no. 6873, 2002, 14 February, 2002, pages 813 - 817, XP002221835, ISSN: 0028-0836 *

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