End Group Modification: Efficient Tool for Improving Activity of Antimicrobial Peptide Analogues towards Gram-Positive Bacteria
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End Group Modification : Efficient Tool for Improving Activity of Antimicrobial Peptide Analogues towards Gram-Positive Bacteria. / Jahnsen, Rasmus O; Sandberg-Schaal, Anne; Frimodt-Møller, Niels; Nielsen, Hanne Mørck; Franzyk, Henrik.
In: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Vol. 95, No. Part A, 23.01.2015, p. 40–46.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - End Group Modification
T2 - Efficient Tool for Improving Activity of Antimicrobial Peptide Analogues towards Gram-Positive Bacteria
AU - Jahnsen, Rasmus O
AU - Sandberg-Schaal, Anne
AU - Frimodt-Møller, Niels
AU - Nielsen, Hanne Mørck
AU - Franzyk, Henrik
N1 - Copyright © 2015. Published by Elsevier B.V.
PY - 2015/1/23
Y1 - 2015/1/23
N2 - 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.
AB - 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.
U2 - 10.1016/j.ejpb.2015.01.013
DO - 10.1016/j.ejpb.2015.01.013
M3 - Journal article
C2 - 25622790
VL - 95
SP - 40
EP - 46
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
IS - Part A
ER -
ID: 130643592