Effects of Sequence Length and Composition on Antimicrobial Peptide Action

Antimicrobial peptides are short, cationic, amphiphilic naturally occurring sequences that have selective antimicrobial properties. The proposed mechanism of action for these peptides is through interaction with and disruption of the bacterial membrane. We have investigated the length and amino acid composition dependence of the antimicrobial peptides ponericin L1 and C18G on antimicrobial activity and membrane binding ability. Truncation of the peptide sequence at different points through synthesis allowed for investigation of length, overall hydrophobicity, and net charge on function. Circular dichroism and fluorescence spectroscopy were used to determine the binding affinity and structure of the peptide in the presence of lipid vesicles. All of the L1 derived peptides exhibited the ability to form alpha helices and bind to the lipid membranes to different degrees. The data suggests that the modified peptide (L1A) and the truncated peptides (L1A-13T, L1A-16T, and L1A-21T) work by forming an alpha helix to permeabilize the bacterial membrane and cause bacteriolysis. Alternatively, the C18G derived truncates exhibited a length threshold in their ability to bind membranes with high affinity and form helical structures. Ongoing experiments are probing membrane topography.