Antimicrobial peptides (AMPs) have been an area of great interest, due to the high selectivity of these molecules toward bacterial targets over host cells and the limited development of bacterial resistance to these molecules through evolution. The peptides are known to selectively bind to bacterial cell surfaces through electrostatic interactions as the cell surface is negatively charged while the peptides are cationic. Once bound, the peptides insert into the cell membrane and cause local disruptions of membrane integrity leading to cell death. Previous experiments showed that replacing the Leu residues in the AMP C18G with other naturally occurring hydrophobic residues resulted side-chain dependent activities. This work extends the investigation to non-natural hydrophobic amino acids and the effect on peptide activity. MIC results demonstrated that amino acid substitutions containing long carbon chains increased antimicrobial activity. Intrinsic Trp fluorescence was used to perform binding assays to model lipid vesicles while Trp quenching was used as a reporter of the local environment. TCE quenching was used to determine peptide aggregation state in solution and showed peptide aggregation only with the most hydrophobic non-natural amino acid substitution. Acrylamide quenching demonstrates that hydrophobic peptides are more deeply buried in the anionic lipid bilayers compared to the zwitterionic bilayers. Vesicle leakage experiments confirmed that only the most hydrophobic peptides were able to disrupt lipid vesicles. Hemolysis assays showed a similar trend. Ongoing experiments are being conducted to investigate the secondary structure and depth of insertion into bilayers.

All hydrophobics are not created equal: Effect of non-natural hydrophobic amino acids in the antimicrobial peptide C18G

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.