Allosteric modulators: The new generation of receptor antagonist

被引：56

作者：

Kenakin, T ^{[1
]}

机构：

[1] GlaxoSmithKline Res & Dev, Assay Dev & Compound Profiling, Res Triangle Pk, NC 27709 USA

来源：

MOLECULAR INTERVENTIONS | 2004年 / 4卷 / 04期

关键词：

D O I：

10.1124/mi.4.4.6

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：

Allosteric antagonists modulate the affinity and/or efficacy of agonists for receptors. Although the manner in which this modulation can occur can mimic that of simple competitive antagonists, allosteric antagonists possess unique properties that can present seemingly capricious profiles of antagonism. These unique properties also offer potentially useful patterns for therapeutic utility. This review summarizes methods to detect allosteric antagonism and some special properties of these receptor modulators.

引用

页码：222 / 229

页数：8

共 36 条

[1] THE CHOLINERGIC HYPOTHESIS OF GERIATRIC MEMORY DYSFUNCTION [J].

BARTUS, RT ;

DEAN, RL ;

BEER, B ;

LIPPA, AS .

SCIENCE, 1982, 217 (4558) :408-417

[2] HIV-1-induced cell fusion is mediated by multiple regions within both the viral envelope and the CCR-5 co-receptor [J].

Bieniasz, PD ;

Fridell, RA ;

Aramori, I ;

Ferguson, SSG ;

Caron, MG ;

Cullen, BR .

EMBO JOURNAL, 1997, 16 (10) :2599-2609

[3]

BURGEN ASV, 1981, FED PROC, V40, P2723

[4] The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates [J].

Choe, H ;

Farzan, M ;

Sun, Y ;

Sullivan, N ;

Rollins, B ;

Ponath, PD ;

Wu, LJ ;

Mackay, CR ;

LaRosa, G ;

Newman, W ;

Gerard, N ;

Gerard, C ;

Sodroski, J .

CELL, 1996, 85 (07) :1135-1148

[5] The V3 domain of the HIV-1 gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection [J].

Cocchi, F ;

DeVico, AL ;

GarzinoDemo, A ;

Cara, A ;

Gallo, RC ;

Lusso, P .

NATURE MEDICINE, 1996, 2 (11) :1244-1247

[6] Change in coreceptor use correlates with disease progression in HIV-1-infected individuals [J].

Connor, RI ;

Sheridan, KE ;

Ceradini, D ;

Choe, S ;

Landau, NR .

JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (04) :621-628

[7]

Domingo E, 1997, Prog Drug Res, V48, P99

[8]

EHLERT FJ, 1988, MOL PHARMACOL, V33, P187

[9] SCH-202676: An allosteric modulator of both agonist and antagonist binding to G protein-coupled receptors [J].

Fawzi, AB ;

Macdonald, D ;

Benbow, LL ;

Smith-Torhan, A ;

Zhang, HT ;

Weig, BC ;

Ho, G ;

Tulshian, D ;

Linder, ME ;

Graziano, MP .

MOLECULAR PHARMACOLOGY, 2001, 59 (01) :30-37

[10] THE ENERGY LANDSCAPES AND MOTIONS OF PROTEINS [J].

FRAUENFELDER, H ;

SLIGAR, SG ;

WOLYNES, PG .

SCIENCE, 1991, 254 (5038) :1598-1603

← 1 2 3 4 →