Shen Bingzheng, Cao Zhijian, Li Wenxin, Sabatier Jean-Marc, Wu Yingliang
a State Key Laboratory of Virology, College of Life Science , Wuhan University , Wuhan , China.
b Department of Pharmacy, Renmin Hospital , Wuhan University , Wuhan , China.
Expert Opin Biol Ther. 2017 Sep;17(9):1065-1075. doi: 10.1080/14712598.2017.1346606. Epub 2017 Jul 11.
The effective treatment of autoimmune diseases remains a challenge. Voltage-gated potassium Kv1.3 channels, which are expressed in lymphocytes, are a new therapeutic target for treating autoimmune disease. Consequently, Kv1.3 channel-inhibiting venom-derived peptides are a prospective resource for new drug discovery and clinical application. Area covered: Preclinical and clinical studies have produced a wealth of information on Kv1.3 channel-inhibiting venom-derived peptides, especially from venomous scorpions and sea anemones. This review highlights the advances in screening and design of these peptides with diverse structures and potencies. It focuses on representative strategies for improving peptide selectivity and discusses the preclinical research on those venom-derived peptides as well as their clinical developmental status. Expert opinion: Encouraging results indicate that peptides isolated from the venom of venomous animals are a large resource for discovering immunomodulators that act on Kv1.3 channels. Since the structural diversity of venom-derived peptides determines the variety of their pharmacological activities, the design and optimization of venom-peptides for improved Kv1.3 channel-specificity has been advanced through some representative strategies, such as peptide chemical modification, amino acid residue truncation and binding interface modulation. These advances should further accelerate research, development and the future clinical application of venom-derived peptides selectively targeting Kv1.3 channels.
自身免疫性疾病的有效治疗仍然是一项挑战。在淋巴细胞中表达的电压门控钾通道Kv1.3，是治疗自身免疫性疾病的一个新的治疗靶点。因此，抑制Kv1.3通道的毒液衍生肽是新药发现和临床应用的一个潜在资源。涵盖领域：临床前和临床研究已经产生了大量关于抑制Kv1.3通道的毒液衍生肽的信息，特别是来自毒蝎和海葵的毒液。这篇综述突出了这些具有不同结构和效力的肽在筛选和设计方面的进展。它着重介绍了提高肽选择性的代表性策略，并讨论了那些毒液衍生肽的临床前研究及其临床开发状况。专家观点：令人鼓舞的结果表明，从有毒动物毒液中分离出的肽是发现作用于Kv1.3通道的免疫调节剂的一个巨大资源。由于毒液衍生肽的结构多样性决定了其药理活性的多样性，通过一些代表性策略，如肽化学修饰、氨基酸残基截短和结合界面调节，已经推进了针对改善Kv1.3通道特异性的毒液肽的设计和优化。这些进展应进一步加速选择性靶向Kv1.3通道的毒液衍生肽的研究、开发和未来临床应用。
