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 |
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Authors: | Xiaojuan Hou Qiang Du Renjie Li Mei Zhou Hui Wang Lei Wang Can Guo Tianbao Chen Chris Shaw |
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Institution: | 1. Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast, BT9 7BL UK;2. Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast, BT9 7BL UK
Institute of Biomedical Engineering, School of Geosciences and Info-Physics, Central South University, Changsha, 410083 China |
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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. |
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Keywords: | amphibian antimicrobial cloning mass spectrometer peptides skin |
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