Identification of novel Kv1.3 targeting venom peptides by a single round of autocrine-based selection.
Identification of novel Kv1.3 targeting venom peptides by a single round of autocrine-based selection.
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DOI：
10.1016/j.bbrc.2019.01.014
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发表时间：
2019-02
影响因子：
3.1
通讯作者：
Yaohui Liu;Jiashuo Zhang;Ruikun Wang;Yaxing Wu;Wei Wang;Xiu Xin;Mingjuan Du;Youjia Cao;Hongkai Zhang
中科院分区：
文献类型：
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作者：
Yaohui Liu;Jiashuo Zhang;Ruikun Wang;Yaxing Wu;Wei Wang;Xiu Xin;Mingjuan Du;Youjia Cao;Hongkai Zhang
蛇毒多肽是一种很好的离子通道活性分子来源，被认为是很有前途的药物靶点。然而，挖掘与离子通道相互作用的毒液仍然具有挑战性。以前开发了基于自分泌的高通量选择系统来筛选毒液肽文库，但是该方法包括重复的选择轮次，这可能导致有价值的命中的损失。为了简化选择过程，采用下一代测序在单轮选择后直接鉴定阳性命中。3个新的Kv1.3靶向毒肽的发现证明了改进系统的优势，其中Kappa-thalatoxin-Tas 2a是一个有效的Kv1.3拮抗剂。因此，这种简化的方法是有效的，以确定新的毒液肽的目标离子通道。
Venom peptides are an excellent source of pharmacologically active molecules for ion channels that have been considered as promising drug targets. However, mining venoms that interact with ion channel remains challenging. Previously an autocrine based high throughput selection system was developed to screen venom peptide library but the method includes repetitious selection rounds that may cause loss of valuable hits. To simplify the selection process, next generation sequencing was employed to directly identify the positive hits after a single round of selection. The advantage of the improved system was demonstrated by the discovery of 3 novel Kv1.3 targeting venom peptides among which Kappa-thalatoxin-Tas2a is a potent Kv1.3 antagonist. Therefore, this simplified method is efficient to identify novel venom peptides that target ion channels.