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

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.