Structure/activity relationships of M2 muscarinic allosteric modulators

被引：41
作者：
Mohr, K
Tränkle, C
Holzgrabe, U
机构：
[1] Univ Bonn, Inst Pharm, D-53121 Bonn, Germany
[2] Univ Wurzburg, Inst Pharm, Wurzburg, Germany
来源：
RECEPTORS & CHANNELS | 2003年 / 9卷 / 04期
关键词：
allosteric modulators; M-2-subtype; muscarinic receptors; review; SARs; CARACURINE-V DERIVATIVES; BIS-AMMONIUM COMPOUND; LIGAND-BINDING; ACETYLCHOLINE-RECEPTORS; POSITIVE COOPERATIVITY; SUBTYPE SELECTIVITY; HEPTANE-1,7-BIS(DIMETHYL-3-PHTHALIMIDOPROPYL)AMMONIUM BROMIDE; ANTAGONIST BINDING; HIGH-AFFINITY; COMMON SITE;
D O I：
10.1080/10606820308264
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 modulation of G protein-coupled receptors has been intensively studied at muscarinic acetylcholine receptors. Findings made with archetypal allosteric agents such as gallamine, alcuronium, and bis(ammonio) alkane-type agents revealed that binding of orthosteric ligands that attach to the acetylcholine site can be allosterically decreased or increased or left unaltered in a subtype-selective fashion. Analyses of structure/activity relationships (SARs) help to elucidate the molecular events underlying the allosteric action and they may pilot the development of new allosteric agents with improved properties and therapeutic perspectives. With a focus on SARs, this review illustrates the principles of muscarinic allosteric interactions, gives an overview of SARs in congeners of archetypal allosteric agents, and considers the topology of M-2 muscarinic allosteric interactions that are characterized by divergent binding modes.
引用
收藏
页码：229 / 240
页数：12
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