DE-NOVO DESIGN OF ENZYME-INHIBITORS BY MONTE-CARLO LIGAND GENERATION

被引：79

作者：

GEHLHAAR, DK

MOERDER, KE

ZICHI, D

SHERMAN, CJ

OGDEN, RC

FREER, ST

机构：

[1] AGOURON PHARMACEUT INC, SAN DIEGO, CA 92121 USA

[2] TORREY SCI & TECHNOL INC, SAN DIEGO, CA 92121 USA

[3] NEXAGEN INC, BOULDER, CO 80301 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 03期

关键词：

D O I：

10.1021/jm00003a010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new computational method for the in situ generation of small molecules within the binding site of a protein is described. The method has been evaluated using two well-studied systems, dihydrofolate reductase and thymidylate synthase. The method has also been used to guide improvements to inhibitors of HIV-1 protease. One such improvement resulted in a compound selected for preclinical studies as an antiviral agent against AIDS.

引用

页码：466 / 472

页数：7

共 28 条

[11] A POTENT ANTI-TUMOR QUINAZOLINE INHIBITOR OF THYMIDYLATE SYNTHETASE - SYNTHESIS, BIOLOGICAL PROPERTIES AND THERAPEUTIC RESULTS IN MICE
JONES, TR
CALVERT, AH
JACKMAN, AL
BROWN, SJ
JONES, M
HARRAP, KR
[J]. EUROPEAN JOURNAL OF CANCER, 1981, 17 (01) : 11 - 19
[12] MULTIPLE PEPTIDE-SYNTHESIS METHODS AND THEIR APPLICATIONS
JUNG, G
BECKSICKINGER, AG
[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 1992, 31 (04) : 367 - 383
[13] A GEOMETRIC APPROACH TO MACROMOLECULE-LIGAND INTERACTIONS
KUNTZ, ID
BLANEY, JM
OATLEY, SJ
LANGRIDGE, R
FERRIN, TE
[J]. JOURNAL OF MOLECULAR BIOLOGY, 1982, 161 (02) : 269 - 288
[14] QUINAZOLINE ANTIFOLATE THYMIDYLATE SYNTHASE INHIBITORS - HETEROCYCLIC BENZOYL RING MODIFICATIONS
MARSHAM, PR
HUGHES, LR
JACKMAN, AL
HAYTER, AJ
OLDFIELD, J
WARDLEWORTH, JM
BISHOP, JAM
OCONNOR, BM
CALVERT, AH
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (05) : 1594 - 1605
[15] CRYSTAL-STRUCTURE OF ESCHERICHIA-COLI THYMIDYLATE SYNTHASE CONTAINING BOUND 5-FLUORO-2'-DEOXYURIDYLATE AND 10-PROPARGYL-5,8-DIDEAZAFOLATE
MATTHEWS, DA
APPELT, K
OATLEY, SJ
XUONG, NH
[J]. JOURNAL OF MOLECULAR BIOLOGY, 1990, 214 (04) : 923 - 936
[16] POTENT INHIBITION OF THYMIDYLATE SYNTHASE BY 2 SERIES OF NONCLASSICAL QUINAZOLINES
MCNAMARA, DJ
BERMAN, EM
FRY, DW
WERBEL, LM
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (07) : 2045 - 2051
[17] EQUATION OF STATE CALCULATIONS BY FAST COMPUTING MACHINES
METROPOLIS, N
ROSENBLUTH, AW
ROSENBLUTH, MN
TELLER, AH
TELLER, E
[J]. JOURNAL OF CHEMICAL PHYSICS, 1953, 21 (06) : 1087 - 1092
[18] MOOS WH, 1993, ANNU REP MED CHEM, V28, P315
[19] AUTOMATIC CREATION OF DRUG CANDIDATE STRUCTURES BASED ON RECEPTOR STRUCTURE - STARTING POINT FOR ARTIFICIAL LEAD GENERATION
NISHIBATA, Y
ITAI, A
[J]. TETRAHEDRON, 1991, 47 (43) : 8985 - 8990
[20] CONFIRMATION OF USEFULNESS OF A STRUCTURE CONSTRUCTION PROGRAM BASED ON 3-DIMENSIONAL RECEPTOR STRUCTURE FOR RATIONAL LEAD GENERATION
NISHIBATA, Y
ITAI, A
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (20) : 2921 - 2928

← 1 2 3 →