Candidacidal mechanism of a Leu/Lys‐rich α‐helical amphipathic model antimicrobial peptide and its diastereomer composed of D,L‐amino acids |
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Authors: | Peng Wang Yong Hai Nan Song Yub Shin |
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Institution: | 1. Department of Bio‐Materials, Graduate School, Chosun University, Gwangju 501‐759, Republic of Korea;2. Department of Cellular & Molecular Medicine, School of Medicine, Chosun University, Gwangju 501‐759, Republic of Korea |
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Abstract: | We investigated the mechanism of candidacidal action of a Lys/Leu‐rich α‐helical model antimicrobial peptide (K9L8W) and its diastereomeric peptide (D9‐K9L8W) composed of D ,L ‐amino acids. K9L8W killed completely Candida albicans within 30 min, but D9‐K9L8W killed only 72% of C. albicans even after 100 min. Tryptophan fluorescence spectroscopy indicated that the fungal cell selectivity of D9‐K9L8W is closely correlated with a selective interaction with the negatively charged PC/PE/PI/ergosterol (5:2.5:2.5:1, w/w/w/w) phospholipids, which mimic the outer leaflet of the plasma membrane of C. albicans. K9L8W was able to induce almost 100% calcein leakage from PC/PE/PI/ergosterol (5:2.5:2.5:1, w/w/w/w) liposomes at a peptide:lipid molar ratio of 1:16, whereas D9‐K9L8W caused only 25% dye leakage even at a peptide:lipid molar ratio of 1:2. Confocal laser‐scanning microscopy revealed that FITC‐labeled D9‐K9L8W penetrated the cell wall and cell membrane and accumulated inside the cells, whereas FITC‐labeled K9L8W did not penetrate but associated with the membranes. Collectively, our results demonstrated that the candidacidal activity of K9L8 W and D9‐K9L8W may be due to the transmembrane pore/channel formation or perturbation of the fungal cytoplasmic membranes and the inhibition of intracellular functions, respectively. Finally, D9‐K9L8W with potent anti‐Candida activity but no hemolytic activity may be potentially a useful lead compound for the development of novel antifungal agents. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. |
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Keywords: | Leu/Lys‐rich α ‐helical model antimicrobial peptide diastereomeric peptide candidacidal activity candidacidal mechanism |
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