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• W1925139611 abstract "The emergence of strains of multidrug‐resistant Gram‐negative bacteria mandates a search for new types of antimicrobial agents. Alyteserin‐2a (ILGKLLSTAAGLLSNL.NH 2 ) is a cationic, α ‐helical peptide, first isolated from skin secretions of the midwife toad, Alytes obstetricans , which displays relatively weak antimicrobial and haemolytic activities. Increasing the cationicity of alyteserin‐2a while maintaining amphipathicity by the substitution Gly 11 → Lys enhanced the potency against both Gram‐negative and Gram‐positive bacteria by between fourfold and 16‐fold but concomitantly increased cytotoxic activity against human erythrocytes by sixfold (mean concentration of peptide producing 50% cell death; LC 50 = 24 µ m ). Antimicrobial potency was increased further by the additional substitution Ser 7 →Lys, but the resulting analogue remained cytotoxic to erythrocytes (LC 50 = 38 µ m ). However, the peptide containing d ‐lysine at positions 7 and 11 showed high potency against a range of Gram‐negative bacteria, including multidrug‐resistant strains of Acinetobacter baumannii and Stenotrophomonas maltophilia (minimum inhibitory concentration = 8 µ m ) but appreciably lower haemolytic activity (LC 50 = 185 µ m ) and cytotoxicity against A549 human alveolar basal epithelial cells (LC 50 = 65 µ m ). The analogue shows potential for treatment of nosocomial pulmonary infections caused by bacteria that have developed resistance to commonly used antibiotics. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd." @default.
• W1925139611 created "2016-06-24" @default.
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• W1925139611 date "2012-03-05" @default.
• W1925139611 modified "2023-10-17" @default.
• W1925139611 title "Analogues of the frog skin peptide alyteserin-2a with enhanced antimicrobial activities against Gram-negative bacteria" @default.
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• W1925139611 doi "https://doi.org/10.1002/psc.2397" @default.
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