Structure and function of μ-conotoxins, peptide-based sodium channel blockers with analgesic activity.
Structure and function of μ-conotoxins, peptide-based sodium channel blockers with analgesic activity.
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DOI：
10.4155/fmc.14.107
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发表时间：
2014-10
影响因子：
4.2
通讯作者：
Norton RS
中科院分区：
文献类型：
--
作者：
Green BR;Bulaj G;Norton RS
μ-芋螺毒素阻断电压门控钠通道(VGSC)，并与河豚毒素竞争结合到钠电导孔。早期的工作发现μ-芋螺毒素优先阻断骨骼肌亚型(NaV1.4)。然而，在过去的十年里，μ芋螺毒素的数量和被抑制的VGSC亚型的范围显著增加(NaV1.2、NaV1.3或Nav1.7)。到目前为止，已经鉴定了20个μ-芋螺毒素序列，并对其中几个与VGSC亚型相互作用的关键残基进行了构效关系研究。体内的止痛药和神经肌肉阻断活动驱动了对基因工程亚型特异性的研究。本文综述了μ-芋螺毒素的结构和药理研究，这些研究表明有希望开发NaV1.2的选择性阻滞剂，也可能开发NaV1.1、1.3或1.7的选择性阻滞剂。
μ-Conotoxins block voltage-gated sodium channels (VGSCs) and compete with tetrodotoxin for binding to the sodium conductance pore. Early efforts identified μ-conotoxins that preferentially blocked the skeletal muscle subtype (NaV1.4). However, the last decade witnessed a significant increase in the number of μ-conotoxins and the range of VGSC subtypes inhibited (NaV1.2, NaV1.3 or NaV1.7). Twenty μ-conotoxin sequences have been identified to date and structure–activity relationship studies of several of these identified key residues responsible for interactions with VGSC subtypes. Efforts to engineer-in subtype specificity are driven by in vivo analgesic and neuromuscular blocking activities. This review summarizes structural and pharmacological studies of μ-conotoxins, which show promise for development of selective blockers of NaV1.2, and perhaps also NaV1.1,1.3 or 1.7.
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