End Group Modification: Efficient Tool for Improving Activity of Antimicrobial Peptide Analogues towards Gram-Positive Bacteria
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
|Tidsskrift||European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V|
|Udgave nummer||Part A|
|Status||Udgivet - 23 jan. 2015|