title: Molecular properties and structure-function relationships of lethal peptides from venom of Wagler's pit viper, Trimeresurus wagleri.
abstract: Two new lethal peptides (waglerins) were purified from the venom of Trimeresurus wagleri, and sequenced. We found them to be analogs of lethal peptides (waglerins) I and II reported previously (Weinstein et al., Toxicon 29, 227-236, 1991), with an additional Ser-Leu on the amino terminus. Three of the four waglerins were synthesized and the products were chemically and biologically equivalent to the naturally occurring counterparts in venom. Murine i.p. LD50 for synthetic waglerins I, SL-I and II were 0.33, 0.22, and 0.51 mg/kg, respectively. The single, intramolecular disulfide bond in each synthetic peptide formed rapidly in high yield. The reduced (cysteine-containing) forms of the peptides appeared to have significant toxicities, even without prior disulfide bond formation, but synthetic analogs with serine substituted for cysteine were not toxic. The synthetic dimer of waglerin I, formed by two intermolecular disulfide bonds, was not toxic, but rapidly rearranged to lethal, monomeric waglerin I at alkaline pH upon the addition of 5 mM beta-mercaptoethanol. Waglerin I was inactivated by cleavage at Tyr-15 with chymotrypsin.
authors.affiliation: Pathophysiology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011.
authors.forename: J J
authors.initials: JJ
authors.lastname: Schmidt
authors.forename: S A
authors.initials: SA
authors.lastname: Weinstein
authors.forename: L A
authors.initials: LA
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin; D003435:Crotalid Venoms / Q000737:chemistry* / Q000633:toxicity; D005260:Female; D006868:Hydrolysis; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000633:toxicity; D014757:Viper Venoms / Q000737:chemistry* / Q000633:toxicity
chemical_list: D003435:Crotalid Venoms; D010455:Peptides; D014757:Viper Venoms; C077895:waglerin; D002918:Chymotrypsin