Muscarinic acetylcholine receptor modulators derived from natural toxins and diverse interaction modes  

作　　者：XU JianRong WANG Hao CHEN HongZhuan 

机构地区：[1]Department of Pharmacology, Institute of Medical Sciences, School of Medicine, Shanghai Jiao Tong University

出　　处：《Science China Chemistry》2013年第10期1333-1343,共11页中国科学（化学英文版）

基　　金：supported by the National Basic Research Program of China(973 Program,2010CB529806);the International Science&Technology Cooperation Program of China(2011DFA33180)

摘　　要：Muscarinic acetylcholine receptors （mAChRs） play crucial roles in various physiological functions and pathophysiological processes. Acetylcholine （ACh）, as a classical ligand and one of the pivotal neurotransmitters, serves as a prototype for the elucidation of molecular interaction and the development of mimicked and antagonized agents. With the advances in medicinal chemistry and structural biology, more and more mAChRs modulators derived from natural toxins have been identified. Based on the chemical structures and the receptor-ligand interaction modes, these mAChRs modulators can be divided into orthosteric modulators, allosteric modulators and other modulators. Moreover, allosteric modulators can be further divided into three groups： alcuronium-like modulators, staurosporine-like modulators, and phlegrnarine-like modulators. In this review, we focus on various mAChRs modulators derived from natural toxins on the basis of the receptor-ligand interaction modes. The under- standing of the affinity, the intrinsic efficacy, and the selectivity of mAChRs modulators may lead to the discovery of new drug leads for the treatment of diseases related to mAChRs.Muscarinic acetylcholine receptors(mAChRs)play crucial roles in various physiological functions and pathophysiological processes.Acetylcholine(ACh),as a classical ligand and one of the pivotal neurotransmitters,serves as a prototype for the elucidation of molecular interaction and the development of mimicked and antagonized agents.With the advances in medicinal chemistry and structural biology,more and more mAChRs modulators derived from natural toxins have been identified.Based on the chemical structures and the receptor-ligand interaction modes,these mAChRs modulators can be divided into orthosteric modulators,allosteric modulators and other modulators.Moreover,allosteric modulators can be further divided into three groups:alcuronium-like modulators,staurosporine-like modulators,and phlegmarine-like modulators.In this review,we focus on various mAChRs modulators derived from natural toxins on the basis of the receptor-ligand interaction modes.The understanding of the affinity,the intrinsic efficacy,and the selectivity of mAChRs modulators may lead to the discovery of new drug leads for the treatment of diseases related to mAChRs.

关 键 词：muscarinic acetylcholine receptor orthosteric modulators allosteric modulators muscarinic toxins GPCR 

分 类 号：R96[医药卫生—药理学]