Walter and Eliza Hall Institute of Medical Research, Victoria, Australia.
Molecules. 2010 Apr 19;15(4):2825-44. doi: 10.3390/molecules15042825.
Voltage-gated sodium channels (VGSCs) contain a specific binding site for a family of cone shell toxins known as mu-conotoxins. As some VGSCs are involved in pain perception and mu-conotoxins are able to block these channels, mu-conotoxins show considerable potential as analgesics. Recent studies have advanced our understanding of the three-dimensional structures and structure-function relationships of the mu-conotoxins, including their interaction with VGSCs. Truncated peptide analogues of the native toxins have been created in which secondary structure elements are stabilized by non-native linkers such as lactam bridges. Ultimately, it would be desirable to capture the favourable analgesic properties of the native toxins, in particular their potency and channel sub-type selectivity, in non-peptide mimetics. Such mimetics would constitute lead compounds in the development of new therapeutics for the treatment of pain.
电压门控钠离子通道 (VGSCs) 含有一个特定的结合位点，用于一组称为 µ 型 conotoxin 的圆锥贝壳毒素。由于某些 VGSCs 参与疼痛感知，而 µ 型 conotoxin 能够阻断这些通道，因此 µ 型 conotoxin 作为镇痛药具有相当大的潜力。最近的研究提高了我们对 µ 型 conotoxin 的三维结构和结构-功能关系的理解，包括它们与 VGSCs 的相互作用。已经创建了天然毒素的截断肽类似物，其中二级结构元件通过非天然连接子（如内酰胺桥）稳定。最终，理想情况下是在非肽模拟物中捕获天然毒素的有利镇痛特性，特别是它们的效力和通道亚型选择性。此类模拟物将成为开发用于治疗疼痛的新型治疗药物的先导化合物。
Zotero 插件
