Structure-function studies of waglerin I, a lethal peptide from the venom of Wagler's pit viper, Trimeresurus wagleri.
Waglerins are 22-24 residue lethal peptides, found in the venom of Trimeresurus (Tropidolaemus) wagleri. The effects upon lethality and immunoreactivity resulting from structural modifications of these peptides were studied. A synthetic analogue with alanine residues in place of the two half-cystines of native peptide was nontoxic, suggesting that the single intramolecular disulfide bond in waglerins is critical for bioactivity. Substituting glutamic acid for aspartic acid at residue 5 slightly diminished lethality. Analogues containing asparagine instead of aspartic acid at residue 5 and/or a carboxamide- instead of a carboxy-terminus were lethal, demonstrating that neither a negative charge on residue 5 nor on the carboxy-terminus was required for bioactivity. A proteolytic fragment of waglerin I containing residues 6-22 was isolated and proved nontoxic. Therefore, one or more of the first five residues were necessary for bioactivity. Antiserum against waglerin I bound strongly to waglerins I, II, and SL-I, and to various analogues, proteolytic fragments, and chemically modified waglerin I. These findings suggest that the antibodies might be directed mainly against short, linear epitopes, implying an extended conformation for waglerin I.
Toxinology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702-5011, USA.
J J
JJ
Schmidt
S A
SA
Weinstein
D000595:Amino Acid Sequence; D000818:Animals; D003435:Crotalid Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D006868:Hydrolysis; D007928:Lethal Dose 50; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D012697:Serine Endopeptidases / Q000494:pharmacology; D013329:Structure-Activity Relationship; D017841:Trimeresurus
D003435:Crotalid Venoms; D010455:Peptides; C077895:waglerin; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase