Effect of detergent on "promiscuous" inhibitors

被引：198

作者：

Ryan, AJ ^{[1
]}

Gray, NM ^{[1
]}

Lowe, PN ^{[1
]}

Chung, CW ^{[1
]}

机构：

[1] GlaxoSmithKline, Computat & Struct Sci, Stevenage SG1 2NY, Herts, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 16期

关键词：

D O I：

10.1021/jm0340896

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The term "promiscuous" inhibitors has been coined for compounds whose inhibition mechanism involves the interaction of aggregates of many compound molecules with the target protein, rather than the binding of individual molecules. This paper demonstrates that promiscuous inhibitors can be differentiated from classical 1:1 inhibitors by the judicious use of detergents, making it possible to configure assays that significantly reduce this undesirable mechanism of inhibition without compromising assay performance.

引用

页码：3448 / 3451

页数：4

共 9 条

[1] THE BETA-LACTAMASE OF ENTEROBACTER-CLOACAE-P99 - CHEMICAL-PROPERTIES, N-TERMINAL SEQUENCE AND INTERACTION WITH 6-BETA-HALOGENOPENICILLANATES [J].

JORIS, B ;

DEMEESTER, F ;

GALLENI, M ;

RECKINGER, G ;

COYETTE, J ;

FRERE, JM ;

VANBEEUMEN, J .

BIOCHEMICAL JOURNAL, 1985, 228 (01) :241-248

[2] Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings [J].

Lipinski, CA ;

Lombardo, F ;

Dominy, BW ;

Feeney, PJ .

ADVANCED DRUG DELIVERY REVIEWS, 1997, 23 (1-3) :3-25

[3] EVOLUTION OF AN ENZYME-ACTIVITY - CRYSTALLOGRAPHIC STRUCTURE AT 2-ANGSTROM RESOLUTION OF CEPHALOSPORINASE FROM THE AMPC GENE OF ENTEROBACTER-CLOACAE-P99 AND COMPARISON WITH A CLASS-A PENICILLINASE [J].

LOBKOVSKY, E ;

MOEWS, PC ;

LIU, HS ;

ZHAO, HC ;

FRERE, JM ;

KNOX, JR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (23) :11257-11261

[4] CRYSTALLOGRAPHIC STRUCTURE OF A PHOSPHONATE DERIVATIVE OF THE ENTEROBACTER-CLOACAE P99 CEPHALOSPORINASE - MECHANISTIC INTERPRETATION OF A BETA-LACTAMASE TRANSITION-STATE ANALOG [J].

LOBKOVSKY, E ;

BILLINGS, EM ;

MOEWS, PC ;

RAHIL, J ;

PRATT, RF ;

KNOX, JR .

BIOCHEMISTRY, 1994, 33 (22) :6762-6772

[5] Kinase inhibitors: Not just for kinases anymore [J].

McGovern, SL ;

Shoichet, BK .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (08) :1478-1483

[6] A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening [J].

McGovern, SL ;

Caselli, E ;

Grigorieff, N ;

Shoichet, BK .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (08) :1712-1722

[7] Simple selection criteria for drug-like chemical matter [J].

Muegge, I ;

Heald, SL ;

Brittelli, D .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (12) :1841-1846

[8]

NEUGEBAUER JM, 1990, METHOD ENZYMOL, V182, P239

[9] Recognizing molecules with drug-like properties [J].

Walters, WP ;

Murcko, A ;

Murcko, MA .

CURRENT OPINION IN CHEMICAL BIOLOGY, 1999, 3 (04) :384-387

← 1 →