An updated unified pharmacophore model of the benzodiazepine binding site on γ-aminobutyric Acida receptors:: Correlation with comparative models

被引：57

作者：

Clayton, T. ^{[1
]}

Chen, J. L. ^{[1
]}

Ernst, M. ^{[4
]}

Richter, L. ^{[4
,5
]}

Cromer, B. A. ^{[2
]}

Morton, C. J. ^{[2
]}

Ng, H. ^{[2
]}

Kaczorowski, C. C. ^{[1
]}

Helmstetter, F. J. ^{[2
]}

Furtmueller, R.

Ecker, G.

Parker, M. W. ^{[3
]}

Sieghart, W. ^{[4
]}

Cook, J. M. ^{[1
]}

机构：

[1] Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53201 USA

[2] Univ Wisconsin, Dept Psychol, Milwaukee, WI 53201 USA

[3] St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia

[4] Med Univ Viennaa, Ctr Brain Res, Div Biochem & Mol Biol, A-1090 Vienna, Austria

[5] Univ Vienna, Dept Med Chem, A-1090 Vienna, Austria

来源：

CURRENT MEDICINAL CHEMISTRY | 2007年 / 14卷 / 26期

关键词：

aminobutyric acid(A) receptors; gated ion channels; GABA-A; computer-assisted analysis; benzodiazepine;

D O I：

10.2174/092986707782360097

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：

A successful unified pharmacophore/receptor model which has guided the synthesis of subtype selective compounds is reviewed in light of recent developments both in ligand synthesis and structural studies of the binding site itself. The evaluation of experimental data in combination with a comparative model of the alpha 1 beta 2 gamma 2 GABA(A) receptor leads to an orientation of the pharmacophore model within the Bz BS. Results not only are important for the rational design of selective ligands, but also for the identification and evaluation of possible roles which specific residues may have within the benzodiazepine binding pocket.

引用

页码：2755 / 2775

页数：21

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