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. (11th August 2014)

• Record Type: Journal Article
• Authors: Hou, Xiaojuan; Du, Qiang; Li, Renjie; Zhou, Mei; Wang, Hui; Wang, Lei; Guo, Can; Chen, Tianbao; Shaw, Chris
• Is Part Of: Chemical biology & drug design. Volume 85:Number 3(2015:Mar.)
• Page Start: 259
• Page End: 267
• Publication Date: 2014-08-11
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12396
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12396-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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, <italic>Bombina variegata</italic>. 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 <italic>Bombina orientalis</italic>. Synthetic feleucin‐BO1 displayed activity against a reference Gram‐positive bacterium. <italic>Staphylococcus aureus</italic> (MIC 34 <italic>μ</italic><sc>m</sc>) but was inactive (> 250 <italic>μ</italic><sc>m</sc>) against the Gram‐negative bacterium, <italic>Escherichia coli</italic>, and the yeast, <italic>Candida albicans</italic>. 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 <italic>μ</italic><sc>m</sc> (<italic>S. aureus</italic>), 14 <italic>μ</italic><sc>m</sc> (<italic>E. coli</italic>) and 7 <italic>μ</italic><sc>m</sc> (<italic>C. albicans</italic>). 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.</p> </abstract>