Title:
STRUCTURAL COORDINATE OF PROTEIN COMPLEX AND UTILIZATION OF THE STRUCTURAL COORDINATE
Document Type and Number:
WIPO Patent Application WO/2001/066593
Kind Code:
A1
Abstract:
A three-dimensional structural coordinate of a protein complex consisting of leptin and a domain of leptin receptor binding to leptin. Use of this structural coordinate makes it possible to identify, search for, evaluate or design leptin mutants, which have a biological activity higher than that of natural leptin or a leptin inhibitory activity, obtained by the substitution, deletion, insertion or chemical modification of one or more amino acid residues, agonists which are compounds having a biological activity comparable or even superior to that of leptin, and antagonists which are compounds inhibiting the biological activity of leptin.
Inventors:
TOH HIROYUKI (JP)
HIROIKE TAKAAKI (JP)
ARITOMI MASAHARU (JP)
KUNISHIMA NAOKI (JP)
MORIKAWA KOSUKE (JP)
HIROIKE TAKAAKI (JP)
ARITOMI MASAHARU (JP)
KUNISHIMA NAOKI (JP)
MORIKAWA KOSUKE (JP)
Application Number:
PCT/JP2001/001666
Publication Date:
September 13, 2001
Filing Date:
March 05, 2001
Export Citation:
Assignee:
BIOMOLECULAR ENGINEERING RES I (JP)
TOH HIROYUKI (JP)
HIROIKE TAKAAKI (JP)
ARITOMI MASAHARU (JP)
KUNISHIMA NAOKI (JP)
MORIKAWA KOSUKE (JP)
TOH HIROYUKI (JP)
HIROIKE TAKAAKI (JP)
ARITOMI MASAHARU (JP)
KUNISHIMA NAOKI (JP)
MORIKAWA KOSUKE (JP)
International Classes:
C07K14/575; C07K14/72; C12N15/12; G01N33/74; G16B15/30; (IPC1-7): C07K14/47; C07K14/705; G01N33/50; G01N33/15; C12N15/12; G06F19/00
Domestic Patent References:
| WO1997020933A2 | 1997-06-12 | |||
| WO1998013781A1 | 1998-04-02 |
Other References:
T. HIROIKE ET AL.: "Homology modeling of human leptin/leptin receptor complex", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 275, no. 11, August 2000 (2000-08-01), pages 154 - 158, XP002947277
A.B.W. SANDRA ET AL.: "A human leptin mutant induces weight gain in normal mice", FEBS LETTERS, vol. 405, 1997, pages 237 - 240, XP002947278
J.E. LAYTON ET AL.: "Identification of a ligand-binding site on the granulocyte colony-stimulating factor receptor by molecular modeling and mutagenesis", J. BIOL. CHEM., vol. 272, no. 47, 1997, pages 29735 - 29741, XP002947279
S.W. FESIK: "NMR structure-based drug design", J. BIOMOLECULAR NMR, vol. 3, no. 3, 1993, pages 261 - 269, XP002947280
J.H. VANDRIE ET AL.: "ALADDIN: An integrated tool for computer-assisted molecular design and pharmacophore recognition from geometric, steric and substructure seaching of three-dimensional molecular structure", J. COMPUT. -AIDED MOL. DES., vol. 3, no. 3, 1989, pages 225 - 251, XP002947281
AKIKO SAKAI: "Computer yakubutsu sekkei wa ima", PHARMACIA, vol. 36, no. 1, January 2000 (2000-01-01), pages 44 - 47, XP002947282
HIDEAKI UMEYAMA: "Yakubutsu sekkei wo shikou shita tanpakushitsu modeling", PHARMACIA, vol. 31, no. 2, 1995, pages 153 - 155, XP002947283
W.F.V. GUNSTEREN ET AL.: "Fundamentals of drug design from a biophysical viewpoint", Q. REV. BIOPHYS., vol. 27, no. 4, 1994, pages 435 - 481, XP002947284
E. SUN ET AL.: "Computer-assisted molecular design and pharmacophore recognition from geometric, steric and substructure searching of three-dimensional molecular structure", GENE, vol. 137, no. 1, 1993, pages 225 - 251, XP002947285
A.B.W. SANDRA ET AL.: "A human leptin mutant induces weight gain in normal mice", FEBS LETTERS, vol. 405, 1997, pages 237 - 240, XP002947278
J.E. LAYTON ET AL.: "Identification of a ligand-binding site on the granulocyte colony-stimulating factor receptor by molecular modeling and mutagenesis", J. BIOL. CHEM., vol. 272, no. 47, 1997, pages 29735 - 29741, XP002947279
S.W. FESIK: "NMR structure-based drug design", J. BIOMOLECULAR NMR, vol. 3, no. 3, 1993, pages 261 - 269, XP002947280
J.H. VANDRIE ET AL.: "ALADDIN: An integrated tool for computer-assisted molecular design and pharmacophore recognition from geometric, steric and substructure seaching of three-dimensional molecular structure", J. COMPUT. -AIDED MOL. DES., vol. 3, no. 3, 1989, pages 225 - 251, XP002947281
AKIKO SAKAI: "Computer yakubutsu sekkei wa ima", PHARMACIA, vol. 36, no. 1, January 2000 (2000-01-01), pages 44 - 47, XP002947282
HIDEAKI UMEYAMA: "Yakubutsu sekkei wo shikou shita tanpakushitsu modeling", PHARMACIA, vol. 31, no. 2, 1995, pages 153 - 155, XP002947283
W.F.V. GUNSTEREN ET AL.: "Fundamentals of drug design from a biophysical viewpoint", Q. REV. BIOPHYS., vol. 27, no. 4, 1994, pages 435 - 481, XP002947284
E. SUN ET AL.: "Computer-assisted molecular design and pharmacophore recognition from geometric, steric and substructure searching of three-dimensional molecular structure", GENE, vol. 137, no. 1, 1993, pages 225 - 251, XP002947285
Attorney, Agent or Firm:
Aoyama, Tamotsu (3-7 Shiromi 1-chom, Chuo-ku Osaka-shi Osaka, JP)
Download PDF: