Insights into the membrane interaction mechanism and antibacterial properties of chensinin-1b
Insights into the membrane interaction mechanism and antibacterial properties of chensinin-1b
复制标题
深入了解chensinin-1b的膜相互作用机制和抗菌特性
DOI：
10.1016/j.biomaterials.2014.10.041
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发表时间：
2015-01-01
期刊：
影响因子：
14
通讯作者：
Shang, Dejing
中科院分区：
文献类型：
--
作者：
Sun, Yue;Dong, Weibing;Shang, Dejing
Antimicrobial peptides (AMPs) with non-specific membrane disrupting activities are thought to exert their antimicrobial activity as a result of their cationicity, hydrophobicity and alpha-helical or beta-sheet structures. Chensinin-1, a native peptide from skin secretions of Rana chensinensis, fails to manifest its desired biological properties because its low hydrophobic nature and an adopted random coil structure in a membrane-mimetic environment. In this study, chensinin-lb was designed by rearranging the amino acid sequence of its hydrophilic/polar residues on one face and its hydrophobic/nonpolar residues on the opposite face according to its helical diagram, and by replacing three Gly residues with three Trp residues. Introduction of Trp residues significantly promoted the binding of the peptide to the bacterial outer membrane and exerted bactericidal activity through cytoplasmic membrane damage. Chensinin-lb demonstrates higher antimicrobial activity and greater cell selectivity than its parent peptide, chensinin-1. The electrostatic interactions between chensinin-lb and lipopolysaccharide (LPS) may have facilitated the uptake of the peptide into Gram-negative cells and be also helpful to disrupt the bacterial cytoplasmic membrane, as evidenced by depolarisation of the membrane potential and leakage of calceins from the liposomes of Escherichia coli and Staphylococcus aureus. Chensinin-lb was also found to penetrate mouse skin and was also effective in vivo, as measured by hydroxyproline levels in a wound infection mouse model, and could therefore act as an anti-infective agent for wound healing. (C) 2014 Elsevier Ltd. All rights reserved.
