ImKTx88, a novel selective Kv1.3 channel blocker derived from the scorpion Isometrus maculates
ImKTx88, a novel selective Kv1.3 channel blocker derived from the scorpion Isometrus maculates
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ImKTx88，一种源自蝎子 Isometrus maculates 的新型选择性 Kv1.3 通道阻断剂
DOI：
10.1016/j.toxicon.2010.12.015
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发表时间：
2011-02-01
期刊：
影响因子：
2.8
通讯作者：
He, Xiaohua
中科院分区：
文献类型：
--
作者：
Han, Song;Hu, Youtian;He, Xiaohua
蝎子毒素是研究离子通道结构和功能的有用物质，也是药物设计的宝贵资源。Kv1.3通道是治疗T细胞介导的自身免疫性疾病的重要药理靶点，近年来许多针对Kv1.3的毒素被确定为良好的候选药物。本研究通过构建cDNA文库的方法，从斑点蝎毒中分离到一个新的毒素基因ImKTx88，并对其进行了纯化和生理活性鉴定。序列分析表明，ImKTx88成熟肽含有39个氨基酸残基，含6个半胱氨酸，可能是α-KTX蝎子家族的一个新成员。电生理实验进一步表明，rImKTx88肽具有一种新的药理特性：它抑制Kv1.3通道电流，IC50为91+/-42 pm，对Kv13的选择性分别为Kv1.1(4200倍)和Kv1.2(93000倍)。以上结果提示，ImKTx88多肽作为一种新型的选择性Kv1.3通道阻滞剂，有望成为治疗自身免疫性疾病的候选药物。(C)2010爱思唯尔有限公司。保留所有权利。
Scorpion toxins are useful in the structure-function research of ion channels and valuable resources for drug design. The Kv1.3 channel is an important pharmacological target for the therapy of T cell-mediated autoimmune diseases, and many toxin peptides targeting Kv1.3 have been identified as good drug candidates in recent years. In this study, a novel toxin gene ImKTx88 was isolated from the venom of the scorpion Isometrus maculates through the construction of the cDNA library method, and the recombinant toxin peptide was purified and characterized physiologically. The mature peptide of ImKTx88 contained 39 amino acid residues including six cysteines and was predicted to be a new member of alpha-KTx scorpion family by sequence analysis. The electrophysiological experiments further indicated that the rImKTx88 peptide had a novel pharmacological profile: it inhibited Kv1.3 channel current with an IC50 of 91 +/- 42 pM, and exhibited very good selectivity for Kv13 over Kv1.1 (4200-fold) and Kv1.2 (93000-fold) channels, respectively. All these results suggested that, as a new selective Kv1.3 channel blocker, the ImKTx88 peptide may serve as a potential drug candidate in the therapy of autoimmune diseases. (c) 2010 Elsevier Ltd. All rights reserved.