Alpha-conotoxins as pharmacological probes of nicotinic acetylcholine receptors.
Alpha-conotoxins as pharmacological probes of nicotinic acetylcholine receptors.
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DOI：
10.1038/aps.2009.47
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发表时间：
2009-06
影响因子：
8.2
通讯作者：
McIntosh, J. Michael
中科院分区：
文献类型：
--
作者：
Azam, Layla;McIntosh, J. Michael
关键词：
来自芋螺（Conus）毒液的富含半胱氨酸的肽靶向多种不同的离子通道。芋螺肽的一个家族，即α-芋螺毒素，特异性地靶向在神经肌肉接头和中枢神经系统中发现的烟碱型乙酰胆碱受体（nAChRs）的不同亚型。这个家族根据半胱氨酸残基之间的氨基酸数量进一步分为亚家族。某些α-芋螺毒素的精妙亚型选择性对于参与神经递质释放调节、帕金森病病理生理学和伤害感受的天然nAChR亚型的表征至关重要。α-芋螺毒素的结构/功能表征已促使开发出效力提高和/或亚型选择性增强的类似物。主链结构的环化以及亲脂性部分的添加提高了α-芋螺毒素的稳定性和生物利用度，从而为口服治疗药物铺平了道路。系统发育、外基因组学和分子建模方面的最新进展有望发现更多的α-芋螺毒素以及对nAChRs特定亚型选择性提高的类似物。
Cysteine-rich peptides from the venom of cone snails (Conus) target a wide variety of different ion channels. One family of conopeptides, the α-conotoxins, specifically target different isoforms of nicotinic acetylcholine receptors (nAChRs) found both in the neuromuscular junction and central nervous system. This family is further divided into subfamilies based on the number of amino acids between cysteine residues. The exquisite subtype selectivity of certain α-conotoxins has been key to the characterization of native nAChR isoforms involved in modulation of neurotransmitter release, the pathophysiology of Parkinson’s disease and nociception. Structure/function characterization of α-conotoxins has led to the development of analogs with improved potency and/or subtype-selectivity. Cyclization of the backbone structure and addition of lipophilic moieties has led to improved stability and bioavailability of α-conotoxins, thus paving the way for orally available therapeutics. The recent advances in phylogeny, exogenomics and molecular modeling promises the discovery of an even greater number of α-conotoxins and analogs with improved selectivity for specific subtypes of nAChRs.
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影响因子：
4.8
作者：
Clark, Richard J.;Fischer, Harald;Craik, David J.
通讯作者：
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影响因子：
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DOI：
10.1073/pnas.0504613102
发表时间：
2005-09-27
影响因子：
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作者：
Clark, RJ;Fischer, H;Craik, DJ
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.5
作者：
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通讯作者：
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