title: Kasstasin: A novel potent vasoconstrictor peptide from the skin secretion of the African red-legged running frog, Kassina maculata.
abstract: Amphibian skin secretions are established sources of bioactive peptides. Here we describe the isolation, structural and pharmacological characterisation of a novel vasoconstrictor peptide from the skin secretion of the African hyperoliid frog, Kassina maculata, which exhibits no structural similarity to any known class of amphibian skin peptide. The peptide consists of 21 amino acid residues, FIKELLPHLSGIIDSVANAIK, and is C-terminally amidated. The provisional structure was obtained by MS/MS fragmentation using an Orbitrap mass spectrometer and L/I ambiguities were resolved following molecular cloning of biosynthetic precursor-encoding cDNA. A synthetic replicate of the peptide was found to possess weak antimicrobial and haemolytic activities but was exceptionally effective in constricting the smooth muscle of rat tail artery (EC(50) of 25 pM). In reflection of its exceptional potency in constricting rat arterial smooth muscle, the peptide was named kasstasin, a derivation of Kassina and "stasis" (stoppage of flow). These data illustrate the continuing potential of amphibian skin secretions to provide novel natural peptide templates for biological evaluation.
authors.affiliation: Molecular Therapeutics Research, School of Pharmacy, Queen's University, 97 Lisburn Road, Belfast, BT9 7BL Northern Ireland, UK.
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Li
authors.forename: Wanyu
authors.initials: W
authors.lastname: Feng
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.forename: Chengbang
authors.initials: C
authors.lastname: Ma
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.forename: Martin
authors.initials: M
authors.lastname: Zeller
authors.forename: Martin
authors.initials: M
authors.lastname: Hornshaw
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry; D006461:Hemolysis; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010455:Peptides / Q000737:chemistry*; D011898:Ranidae / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D018076:DNA, Complementary; D010455:Peptides; D014662:Vasoconstrictor Agents; C569657:kasstasin peptide, Kassina maculata