Development of a Photoactivatable Allosteric Ligand for the M1 Muscarinic Acetylcholine Receptor

被引：8

作者：

Davie, Briana J. ^{[1
]}

Sexton, Patrick M. ^{[1
]}

Capuano, Ben ^{[1
]}

Christopoulos, Arthur ^{[1
]}

Scammells, Peter J. ^{[1
]}

机构：

[1] Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia

来源：

ACS CHEMICAL NEUROSCIENCE | 2014年 / 5卷 / 10期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

Muscarinic; allosteric; photoactivatable; photoaffinity; BQCA; cognition; CARBOXYLIC-ACID BQCA; AFFINITY; ANALOGS; SITE;

D O I：

10.1021/cn500173x

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 field of G protein-coupled drug discovery has benefited greatly from the structural and functional insights afforded by photoactivatable ligands. One G protein-coupled receptor subfamily for which photoactivatable ligands have been developed is the muscarinic acetylcholine receptor family, through, to date, all such ligands have been designed to target the orthosteric (endogenous ligand) binding site of these receptors. Herein we report the synthesis and pharmacological investigation of a novel photoaffinity label, MIPS1455 (4), designed to bind irreversibly to an allosteric site of the M-1 muscarinic acetylcholine receptor; a target of therapeutic interest for the treatment of cognitive deficits. MIPS1455 may be a valuable molecular tool for further investigating allosteric interactions at this receptor.

引用

页码：902 / 907

页数：6

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