Wang Ying, Li Xiaojie, Yang Meifeng, Wu Chunyun, Zou Zhirong, Tang Jing, Yang Xinwang
Ethic Drug Screening and Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicine Resource, State Ethnic Affairs Commission and Ministry of Education, Yunnan University of Nationalities, Kunming, 650500, China.
Department of Biochemistry and Molecular Biology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
J Pept Sci. 2017 May;23(5):384-391. doi: 10.1002/psc.2988. Epub 2017 Mar 1.
Pain is a major symptom of many diseases and results in enormous pressures on human body or society. Currently, clinically used analgesic drugs, including opioids and nonsteroidal anti-inflammatory drugs, have adverse reactions, and thus, the development of new types of analgesic drug candidates is urgently needed. Animal venom peptides have proven to have potential as new types of analgesic medicine. In this research, we describe the isolation and characterization of an analgesic peptide from the crude venom of centipede, Scolopendra subspinipes mutilans. The amino acid sequence of this peptide was identical with SsmTX-I that was previously reported as a specific Kv2.1 ion channel blocker. Our results revealed that SsmTX-I was produced by posttranslational processing of a 73-residue prepropeptide. The intramolecular disulfide bridge motifs of SsmTX-I was Cys1-Cys3 and Cys2-Cys4. Functional assay revealed that SsmTX-I showed potential analgesic activities in formalin-induced paw licking, thermal pain, and acetic acid-induced abdominal writhing mice models. Our research provides the first report of cDNA sequences, disulfide motif, successful synthesis, and analgesic potential of SsmTX-I for the development of pain-killing drugs. It indicates that centipede peptide toxins could be a treasure trove for the search of novel analgesic drug candidates. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
疼痛是许多疾病的主要症状，给人体或社会带来巨大压力。目前，临床使用的镇痛药，包括阿片类药物和非甾体抗炎药，都有不良反应，因此，迫切需要开发新型镇痛候选药物。动物毒液肽已被证明有作为新型镇痛药的潜力。在本研究中，我们描述了从少棘蜈蚣粗毒液中分离和鉴定一种镇痛肽的过程。该肽的氨基酸序列与先前报道的作为特异性Kv2.1离子通道阻滞剂的SsmTX-I相同。我们的结果表明，SsmTX-I是由一个73个残基的前原肽经翻译后加工产生的。SsmTX-I的分子内二硫键基序为Cys1-Cys3和Cys2-Cys4。功能测定表明，SsmTX-I在福尔马林诱导的舔足、热痛和醋酸诱导的扭体小鼠模型中显示出潜在的镇痛活性。我们的研究首次报道了SsmTX-I的cDNA序列、二硫键基序、成功合成及其镇痛潜力，为开发止痛药物提供了依据。这表明蜈蚣肽毒素可能是寻找新型镇痛候选药物的宝库。版权所有©2017欧洲肽协会和约翰·威利父子有限公司。
