title: Feleucin-BO1: a novel antimicrobial non-apeptide amide from the skin secretion of the toad, Bombina orientalis, and design of a potent broad-spectrum synthetic analogue, feleucin-K3.
abstract: Feleucins-BV1 and -BV2 are recently described prototypes of a novel antimicrobial non-apeptide (AMP) family identified in the skin secretion of the bombinid toad, Bombina variegata. They are encoded on different precursors that also encode a novel bombinin. Here we describe the identification of feleucin-BO1 (FLGLLGSLLamide) which is co-encoded with a different novel bombinin, named feleucin precursor-associated bombinin (FPA-bombinin-BO), from the skin secretion of Bombina orientalis. Synthetic feleucin-BO1 displayed activity against a reference Gram-positive bacterium. Staphylococcus aureus (MIC 34 μm) but was inactive (> 250 μm) against the Gram-negative bacterium, Escherichia coli, and the yeast, Candida albicans. This pattern of activity was similar to that of the prototypes. Design and synthesis of a cationicity-enhanced analogue, feleucin-K3 (F-K3), in which the amino acid residues at positions 3 (G), 6 (G) and 7 (S) of feleucin-BO1 were substituted with Lys (K) residues, resulted in a peptide with significantly enhanced potency and spectrum of activity. The MICs of F-K3 against the reference micro-organisms were 7 μm (S. aureus), 14 μm (E. coli) and 7 μm (C. albicans). These data indicate that the skin secretions of amphibians can continue to provide novel peptide templates for the rational design of analogues with possible therapeutic utility.
authors: School of Pharmaceutical Sciences, China Medical University, Shenyang, Liaoning, 110001, China; Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast, BT9 7BL, UK.
authors: Xiaojuan
authors: X
authors: Hou
authors: Qiang
authors: Q
authors: Du
authors: Renjie
authors: R
authors: Li
authors: Mei
authors: M
authors: Zhou
authors: Hui
authors: H
authors: Wang
authors: Lei
authors: L
authors: Wang
authors: Can
authors: C
authors: Guo
authors: Tianbao
authors: T
authors: Chen
authors: Chris
authors: C
authors: Shaw
mesh_terms: D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001001:Anura; D002176:Candida albicans / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D015723:Gene Library; D006461:Hemolysis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D012867:Skin / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects; D053719:Tandem Mass Spectrometry
chemical_list: D000577:Amides; D029845:Amphibian Proteins; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C000602516:feleucin-BO1 peptide, Bombina orientalis
keywords: amphibian; antimicrobial; cloning; mass spectrometer; peptides; skin