Helokinestatin-7 peptides from the venoms of Heloderma lizards

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• 作者：Chengbang Ma^a ; ¹ ; Hui Wang^a ; ¹ ; Yuxin Wu^a ; Mei Zhou^a ; Gemma Lowe^a ; Lei Wang^a ; ^{l.wang@qub.ac.uk} ; Yingqi Zhang^a ; ^b ; ^{zhangyingqi08@sina.com} ; Tianbao Chen^a ; Chris Shaw^a
• 关键词：Lizard ; Venom ; Bradykinin ; Antagonist ; Mass spectrometry ; Molecular cloning ; Peptide
• 刊名：Peptides
• 出版年：2012
• 期刊代码：59_01969781
• 类别：neu
• 出版时间：June, 2012
• 卷：35
• 期：2
• 页码：300-305
• 文件大小：626 K

摘要

Helokinestatins 1-6 constitute a family of bradykinin antagonist peptides originally isolated from the venoms of the Gila Monster, Heloderma suspectum and the Mexican beaded lizard, Heloderma horridum. Here we report the identification, isolation and preliminary pharmacological characterization of two novel tridecapeptides, named helokinestatin-7S (FDDDSTELILEPR - 1550 Da) and helokinestatin-7H (FDDDSRKLILEPR - 1604 Da), whose primary structures were predicted from cDNAs cloned from venom libraries of respective Heloderma lizards. Computed molecular masses of putative helokinestatin-7 peptides were used as tools to locate these peptides in archived LC/MS fractions from respective venoms and sequences were confirmed by MS/MS fragmentation. A synthetic replicate of helokinestatin-7H was found to antagonize the relaxation effect of bradykinin on rat arterial smooth muscle but to have no measurable effects alone. In contrast, synthetic helokinestatin-7S was found to directly contract this preparation. Studies on related natural peptides with subtle differences in primary structure can provide the tools for structure/activity studies in pharmacological investigations directed toward unraveling the molecular basis of venom toxicity and for the evaluation of potential therapeutic leads.