SELECTIVE PHOSPHINATE TRANSITION-STATE ANALOG INHIBITORS OF THE PROTEASE OF HUMAN-IMMUNODEFICIENCY-VIRUS

被引：86

作者：

GROBELNY, D ^{[1
]}

WONDRAK, EM ^{[1
]}

GALARDY, RE ^{[1
]}

OROSZLAN, S ^{[1
]}

机构：

[1] NCI,FREDERICK CANC RES FACIL,BASIC RES PROGRAM,ABL,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21701

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1990年 / 169卷 / 03期

关键词：

D O I：

10.1016/0006-291X(90)92010-W

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The phosphinic acid isosteres of di-, tetra- and hexapeptides containing a hydrophobic amino acid side chains at the P1-P′1 positions are powerful inhibitors of Human Immunodeficiency Virus protease. Ki's ranged from 0.4 nM to 26 μM at pH 6.5 and were lower at pH 4.5. The compounds showed no activity against trypsin, weak activity against renin at pH 6.5, moderate activity against pepsin at pH 2.0 (Ki values in the μM range) and substantial activity against cathepsin D at pH 3.5 (Ki values from 9 to 300 nM). © 1990.

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页码：1111 / 1116

页数：6

相关论文

共 22 条

[1] AN IMPROVED CATHEPSIN-D SUBSTRATE AND ASSAY PROCEDURE [J].

AGARWAL, N ;

RICH, DH .

ANALYTICAL BIOCHEMISTRY, 1983, 130 (01) :158-165

[2] GENETIC-LOCUS, PRIMARY STRUCTURE, AND CHEMICAL SYNTHESIS OF HUMAN IMMUNODEFICIENCY VIRUS PROTEASE [J].

COPELAND, TD ;

OROSZLAN, S .

GENE ANALYSIS TECHNIQUES, 1988, 5 (06) :109-115

[3] HIV-1 PROTEASE SPECIFICITY OF PEPTIDE CLEAVAGE IS SUFFICIENT FOR PROCESSING OF GAG AND POL POLYPROTEINS [J].

DARKE, PL ;

NUTT, RF ;

BRADY, SF ;

GARSKY, VM ;

CICCARONE, TM ;

LEU, CT ;

LUMMA, PK ;

FREIDINGER, RM ;

VEBER, DF ;

SIGAL, IS .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 156 (01) :297-303

[4] THE DETERMINATION OF ENZYME INHIBITOR CONSTANTS [J].

DIXON, M .

BIOCHEMICAL JOURNAL, 1953, 55 (01) :170-171

[5] INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS-1 PROTEASE INVITRO - RATIONAL DESIGN OF SUBSTRATE-ANALOG INHIBITORS [J].

DREYER, GB ;

METCALF, BW ;

TOMASZEK, TA ;

CARR, TJ ;

CHANDLER, AC ;

HYLAND, L ;

FAKHOURY, SA ;

MAGAARD, VW ;

MOORE, ML ;

STRICKLER, JE ;

DEBOUCK, C ;

MEEK, TD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (24) :9752-9756

[6] FLUORIMETRIC ASSAY OF RENIN [J].

GALEN, FX ;

DEVAUX, C ;

GROGG, P ;

MENARD, J ;

CORVOL, P .

BIOCHIMICA ET BIOPHYSICA ACTA, 1978, 523 (02) :485-493

[7] BINDING ENERGETICS OF PHOSPHORUS-CONTAINING INHIBITORS OF THERMOLYSIN [J].

GROBELNY, D ;

GOLI, UB ;

GALARDY, RE .

BIOCHEMISTRY, 1989, 28 (12) :4948-4951

[8]

Henderson L.E., 1988, UCLA S MOL CELL BIOL, V71, P135

[9] LINEAR EQUATION THAT DESCRIBES STEADY-STATE KINETICS OF ENZYMES AND SUBCELLULAR PARTICLES INTERACTING WITH TIGHTLY BOUND INHIBITORS [J].

HENDERSON, PJ .

BIOCHEMICAL JOURNAL, 1972, 127 (02) :321-+

[10] ACTIVE HUMAN IMMUNODEFICIENCY VIRUS PROTEASE IS REQUIRED FOR VIRAL INFECTIVITY [J].

KOHL, NE ;

EMINI, EA ;

SCHLEIF, WA ;

DAVIS, LJ ;

HEIMBACH, JC ;

DIXON, RAF ;

SCOLNICK, EM ;

SIGAL, IS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (13) :4686-4690