作用于烟碱乙酰胆碱受体的α-芋螺毒素研究进展

α~*-Conotoxins Targeting Nicotinic Acetylcholine Receptors

芋螺毒素(conotoxin,conopeptide,CTx)是由热带海洋中的肉食性软体动物芋螺分泌产生的一大类生物活性肽,它们相对分子质量小,能特异地作用于动物体内各种离子通道和受体,具有巨大的药物开发价值。其中,A-超家族的α-芋螺毒素(α-CTx)是发现最早的且最重要的一类成员,它能特异性作用于烟碱型乙酰胆碱受体(nicotinic acetylcholine receptors,nAChRs),是肌肉或神经型nAChRs的选择性阻断剂。nAChRs与中枢神经系统紊乱如疼痛、成瘾、癌症等多种疾病密切相关。近年来,人们陆续发现其他超家族的芋螺毒素中也有成员可阻断nAChRs,如αA-、αB-、αO-、αC-、αD-、αS-等家族的芋螺毒素。上述能阻断nAChRs的芋螺毒素统称为α~*-芋螺毒素(α~*-CTx)。α~*-芋螺毒素对nAChRs阻断活性的差别与它们的结构有着密切的联系。结合国内外研究现状,对α~*-CTx与nAChRs相互作用的关键位点以及结构与功能的关系进行综述,可为相关研究提供参考。

Conotoxins （CTxs） are a group of active peptides from Conus, the tropical marine mollusc. These peptides, with low relative molecular mass, target various ion channels and receptors in animals, and have great potential to be developed into novel drugs. Alpha-conotoxins （α＊-CTxs） are the earliest known and most important members that specifically act on the nicotinic acetylcholine receptors （nAChRs）. They belong to the A-superfamily conotoxins and are selective blockers for muscle or nerve type nAChRs. The nAChRs are closely related with many central nervous system disorders, such as pain, addiction and cancer etc. Recently, other members from other superfamilies are also found to block nAChRs, such as αA-, （xB-, αO-, αC-, αD-, and αS-superfamily conotoxins, and they are named α＊-CTxs. Here, the progress of structure and function characteristics of α＊-CTxs and the receptors, as well as their interactions, were reviewed, which would provide reference for relative research.