Investigating the antimicrobial peptide 'window of activity' using cationic lipopeptides with hydrocarbon and fluorinated tails

International Journal of Antimicrobial Agents
Brandon FindlayFrank Schweizer

Abstract

To probe the effect of carbon-fluorine bonds on antimicrobial peptide-membrane interactions, 24 cationic lipopeptides were created. The collection of lipopeptides was built from two different peptide sequences, KGK and KKK, with a variety of different lipids selected to probe the effectiveness of both hydrocarbon and fluorinated tails. The antimicrobial activity of each peptide was tested against a mixture of pathogenic and reference bacterial strains, with the cationic disinfectant benzalkonium chloride as a positive control. Non-specific interactions with hydrophobic proteins were assessed by repeating antimicrobial testing in the presence of bovine serum albumin (BSA), and the toxicity of the lipopeptides was assessed by measuring lysis of ovine erythrocytes. Peptide sequence had a moderate effect on activity, with the most active peptide (C16-KGK) inhibiting the growth of two Staphylococcus epidermidis strains at ≤ 0.25 μg/mL. Tail composition was less important than the overall hydrophobicity, with the most active fluorinated tails equivalent to moderately active hydrocarbon tails. The activity of all peptides was significantly reduced by the presence of BSA, and haemolysis was closely correlated with antimicrobial activity.

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Citations

Jul 31, 2012·PloS One·Brandon FindlayFrank Schweizer
Jan 25, 2014·BMC Structural Biology·Annfrid SivertsenBjørn Olav Brandsdal
Mar 29, 2014·Journal of Peptide Science : an Official Publication of the European Peptide Society·Annfrid SivertsenMorten B Strøm
Jan 28, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Rasmus O JahnsenHenrik Franzyk
Sep 26, 2015·Journal of Nanobiotechnology·Luccas Missfeldt SanchesAna Maria Carmona-Ribeiro
May 15, 2013·International Journal of Molecular Sciences·Ana Maria Carmona-Ribeiro, Letícia Dias de Melo Carrasco
Jul 3, 2018·Journal of Peptide Science : an Official Publication of the European Peptide Society·Natalia MolchanovaHenrik Franzyk
Sep 11, 2020·Scientific Reports·Natalia MolchanovaHåvard Jenssen
Mar 7, 2017·Frontiers in Neuroscience·Jianguo LiRoger W Beuerman
Aug 4, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Smritilekha BeraFrank Schweizer
Dec 2, 2020·International Journal of Molecular Sciences·Izabela MałuchEmilia Sikorska
Jul 12, 2013·Langmuir : the ACS Journal of Surfaces and Colloids·Alliny F NavesAna M Carmona-Ribeiro

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