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|標題:||Interaction of cationic antimicrobial peptides with phospholipid vesicles and their antibacterial activity||作者:||Chou, H.T.
|關鍵字:||Antimicrobial peptide;Cationic;Liposomes;Phospholipid;Calcein;bovine pancreatic deoxyribonuclease;membrane;resistance;helix;pleurocidin;mechanisms;proteins;bacteria;features;vibrio||Project:||Peptides||期刊/報告no：:||Peptides, Volume 31, Issue 10, Page(s) 1811-1820.||摘要:||
We have designed and synthesized a series of cationic a-helical AMPs with improved antibacterial activity and selectivity against a broad spectrum of G(+) and G(-) bacteria. In the current study, we intended to gain further insight into the mechanisms of action between AMPs and cellular membranes using model liposomes of various phospholipid compositions. Circular dichroism measurements showed that AMPs adopted amphipathic a-helical conformation in the presence of negatively charged vesicles (DOPC/DOPG = 1:3), while they were largely unstructured when incubated with neutral vesicles (DOPC). The interaction of AMPs with phospholipid vesicles were further analyzed by calcein leakage experiments. AMPs exhibited weak dye-leakage activity for DOPC (neutral) vesicles, while they effectively induced calcein leakage when interacted with DOPC/DOPG-entrapped vesicles. These results indicated that our newly designed cationic AMPs did show preferences for bacteria-mimicking anionic membranes. All of them exert their cytolytic activity by folding into an amphipathic helix upon selectively binding and insertion into the target membrane, leading to breakdown of the membrane structure, thus causing leakage of cell contents, resulting finally in cell death. Elucidating the mechanism of the membranolytic activity of AMPs may facilitate the development of more effective antimicrobial agents. (C) 2010 Elsevier Inc. All rights reserved.
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