title: Hylaranins: prototypes of a new class of amphibian antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii.
abstract: Amphibian skin secretions contain a broad spectrum of biologically active compounds, particularly antimicrobial peptides, which are considered to constitute a first line of defence against bacterial infection. Here we describe the identification of two prototype peptides representing a novel structural class of antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii. Named hylaranin-L1 (GVLSAFKNALPGIMKIIVamide) and hylaranin-L2 (GVLSVIKNALPGIMRFIAamide), both peptides consist of 18 amino acid residues, are C-terminally amidated and are of unique primary structures. Their primary structures were initially deduced by MS/MS fragmentation sequencing from reverse-phase HPLC fractions of skin secretion that demonstrated antimicrobial activity. Subsequently, their precursor-encoding cDNAs were cloned from a skin secretion-derived cDNA library and their primary structures were confirmed unequivocally. Synthetic replicates of both peptides exhibited broad-spectrum antimicrobial activity with mean inhibitory concentrations (MICs) of 34 μM against Gram-negative Escherichia coli, 4.3 μM against Gram-positive Staphylococcus aureus and 4-9 μM against the yeast, Candida albicans. Both peptides exhibited little haemolytic activity (<6%) at the MICs for S. aureus and C. albicans. Amphibian skin secretions thus continue to provide novel antimicrobial peptide structures that may prove to be lead compounds in the design of new classes of anti-infection therapeutics.
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Peng
authors.initials: P
authors.lastname: Lyu
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.forename: Suhua
authors.initials: S
authors.lastname: Guo
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D002176:Candida albicans / Q000187:drug effects; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011898:Ranidae / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000737:chemistry* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides