靶向KCNQ的蝎多肽药物设计与研究进展

Design and research progress of scorpion peptide drugs targeting KCNQ

电压门控钾离子通道Kv7.1-Kv7.5(KCNQ1-5)分布于心脏(KCNQ1)、中枢和外周神经元(KCNQ2-KCNQ5),对膜兴奋性有强烈的抑制作用,其功能异常是心脏长QT综合征(long QT syndrome,LQTS)、心房颤动、癫痫和耳聋等多种离子通道病的主因。蝎毒中的神经毒素多肽分子可与电压门控钾通道(voltage-gated potassium channel,Kv)的孔区相互作用,调节或阻滞离子通道电流,选择性强且副作用小。本文综述了蝎多肽与Kv的特性和互作活性表面,通过对比Kv和KCNQ通道孔区结构的差异预测靶向KCNQ通道蝎多肽调节剂的特性,以期为KCNQ特异性多肽新药设计与研发奠定理论基础。

The voltage-gated potassium channels Kv7.1-Kv7.5(KCNQ1-5)are distributed in the heart(KCNQ1),central or peripheral neurons(KCNQ2-KCNQ5).KCNQ has a strong inhibitory effect on membrane excitability.Its abnormal function is the main cause of various ion channel diseases,such as long QT syndrome(LQTS),atrial fibrillation,epilepsy and deafness.The neurotoxin peptide of scorpion venom can interact with the pore region of voltage-gated potassium channel(Kv)to modulate or block ion channel current with strong selectivity and less side effects.In this paper,the characteristics and interactive active surfaces of scorpion peptides and Kv were reviewed.The characteristics of scorpion peptide modulators targeting to KCNQ channels were predicted by comparing the differences of the pore structure between Kv and KCNQ channels.This paper provided a theoretical foundation for the design and development of new KCNQ-specific peptide drugs.