title: Helokinestatin: a new bradykinin B2 receptor antagonist decapeptide from lizard venom.
abstract: Synthetic bradykinin antagonist peptides/peptoids have been powerful tools for delineating the roles of kinins in both normal physiology and in pathological states. Here, we report the identification of a novel, naturally occurring bradykinin B2 receptor antagonist peptide, helokinestatin, isolated and structurally characterized from the venoms of helodermatid lizards-the Gila monster (Heloderma suspectum) and the Mexican beaded lizard (Heloderma horridum). The primary structure of the peptide was established by a combination of microsequencing and mass spectroscopy as Gly-Pro-Pro-Tyr-Gln-Pro-Leu-Val-Pro-Arg (Mr 1122.62). A synthetic replicate of helokinestatin was found to inhibit bradykinin-induced vasorelaxation of phenylephrine pre-constricted rat tail artery smooth muscle, mediated by the B2 receptor sub-type, in a dose-dependent manner. Natural selection, that generates functional optimization of predatory reptile venom peptides, can potentially provide new insights for drug lead design or for normal physiological or pathophysiological processes.
authors: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK. h.f.kwok@qub.ac.uk <h.f.kwok@qub.ac.uk>
authors: Hang Fai
authors: HF
authors: Kwok
authors: Tianbao
authors: T
authors: Chen
authors: Martin
authors: M
authors: O'Rourke
authors: Craig
authors: C
authors: Ivanyi
authors: David
authors: D
authors: Hirst
authors: Chris
authors: C
authors: Shaw
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects; D065094:Bradykinin B2 Receptor Antagonists; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D008116:Lizards; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009842:Oligopeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013997:Time Factors; D014688:Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; D009842:Oligopeptides; D014688:Venoms; C527846:helokinestatin