Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models
Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models
复制标题
具有两个分子内二硫键的蜈蚣毒肽SsmTX-I在动物模型中显示出镇痛活性
DOI：
10.1002/psc.2988
复制
发表时间：
2017
影响因子：
2.1
通讯作者：
Yang Xinwang
中科院分区：
文献类型：
--
作者：
Wang Ying;Li Xiaojie;Yang Meifeng;Wu Chunyun;Zou Zhirong;Tang Jing;Yang Xinwang
疼痛是许多疾病的主要症状，给人体和社会带来巨大的压力。目前，临床使用的镇痛药物，包括阿片类和非甾体抗炎药，存在不良反应，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具有作为新型镇痛药物的潜力。本研究从蜈蚣（Scolopendra subspinipes mutilans）粗毒中分离纯化了一种镇痛肽。该肽的氨基酸序列与先前报道的作为特异性Kv2.1离子通道阻断剂的SsmTX-I相同。我们的研究结果表明，SsmTX-I是由73个残基的前原肽的翻译后加工产生的。SsmTX-I的分子内二硫桥基序为Cys 1-Cys 3和Cys 2-Cys 4。功能测定显示，SsmTX‐I在福尔马林诱导的舔爪、热痛和乙酸诱导的腹部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、成功合成和镇痛潜力，用于开发止痛药物。提示蜈蚣肽类毒素可能是寻找新型镇痛药物的一个宝库。版权所有© 2017 European Peptide Society and John Wiley & Sons，Ltd.
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.