کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2083366 | 1545330 | 2015 | 7 صفحه PDF | دانلود رایگان |
• Structural optimization of antibacterial α-peptide/β-peptoid hybrid oligomers.
• Hydrophobic modification of the N-terminus gives increased antibacterial activity.
• Small moieties were able to confer increased selectivity to the peptide analogues.
• Multidrug-resistant strains of Gram-positive bacteria may be targeted.
Increased incidence of infections with multidrug-resistant bacterial strains warrants an intensive search for novel potential antimicrobial agents. Here, an antimicrobial peptide analogue with a cationic/hydrophobic alternating design displaying only moderate activity against Gram-positive pathogens was optimized. Generally, introduction of hydrophobic moieties at the N-terminus resulted in analogues with remarkably increased activity against multidrug-resistant Staphylococcus aureus and Enterococcus faecium. Interestingly, the potency against Escherichia coli strains was unaffected, whereas modification with hydrophobic moieties led to increased activity towards the Gram-negative Acinetobacter baumannii. Despite increased cytotoxicity against murine fibroblasts and human umbilical vein endothelial cells, the optimized peptide analogues exhibited significantly improved cell selectivity. Overall, the most favorable hydrophobic activity-inducing moieties were found to be cyclohexylacetyl and pentafluorophenylacetyl groups, while the presence of a short PEG-like chain had no significant effect on activity. Introduction of cationic moieties conferred no effect or merely a moderate activity-promoting effect to the analogues.
Figure optionsDownload high-quality image (138 K)Download as PowerPoint slide
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 95, Part A, September 2015, Pages 40–46