A photoreactive probe that differentiates the binding sites of noncompetitive GABA receptor antagonists

被引：6

作者：

Shimotahira, Hiroshi ^{[1
]}

Fusazaki, Sayaka ^{[1
]}

Ikeda, Izumi ^{[1
]}

Ozoe, Yoshihisa ^{[1
]}

机构：

[1] Shimane Univ, Dept Life Sci & Biotechnol, Matsue, Shimane 6908504, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 06期

关键词：

Photoreactive probe; Noncompetitive antagonist; GABA; Picrotoxinin; Fipronil; CYSTEINE MUTANTS; CHLORIDE CHANNEL; POINT MUTATIONS; AMINO-ACID; M2; REGION; PICROTOXIN; SUBUNIT; FIPRONIL; RESIDUES; SENSITIVITY;

D O I：

10.1016/j.bmcl.2011.01.118

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

gamma-Aminobutyric acid (GABA) receptors are postsynaptic membrane protein complexes that are important not only in the regulation of the nervous system but also as targets of drugs and insecticides. We synthesized a photoreactive straight-chain noncompetitive antagonist (NCA), 2-nitro-4-[3-(trifluoromethyl)3H- diazirin-3-yl]phenyl 4-(4-methoxycarbonyl-1-butynyl)benzoate (NMB), to probe the NCA binding site. Our data show that this probe labels the NCA site and demonstrate that the NCA insecticide fipronil binds at a site distinct from that of other NCAs, such as picrotoxinin and 4'-ethynyl-4-n-propyl-bicycloorthobenzoate. The unique molecule NMB will be useful in identifying the cross-linking site of straight-chain NCAs in GABA receptors and mapping allosteric binding sites. Such studies should provide invaluable information in designing novel NCAs. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1598 / 1600

页数：3

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