title: Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Meifeng
authors.identifier: http://orcid.org/0000-0003-3210-8908
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Chunyun
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, China.
authors.forename: Xinwang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001180:Arthropod Venoms / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D001181:Arthropods / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D051379:Mice; D023421:Models, Animal; D059408:Pain Management; D051669:Shab Potassium Channels / Q000037:antagonists & inhibitors*
chemical_list: D000700:Analgesics; D001180:Arthropod Venoms; D004220:Disulfides; D051669:Shab Potassium Channels
keywords: Scolopendra subspinipes mutilans; SsmTX-I; analgesic peptide; centipede venom; disulfide bridge