Selective Antibacterial Activity and Lipid Membrane Interactions of Arginine-Rich Amphiphilic Peptides

The self-assembly behaviour and antimicrobial activity of two new designed amphiphilic peptides, R3F3 and R4F4, containing short hydrophobic phenylalanine (F) cationic arginine (R) sequences are investigated. The conformation of the peptides was examined using circular dichroism and FTIR spectroscopy, which show that they have a disordered secondary structure. Concentration-dependent fluorescence assays show the presence of a critical aggregation concentration (cac) for each peptide. Above the cac, small angle x-ray scattering (SAXS) and transmission electron microscopy (TEM) show the presence of a population of twisted tapes for R3F3 and nanosheets for R4F4. The interaction of the peptides with model bacterial membranes comprising mixtures of the lipids DPPG [1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol)] and DPPE [1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine], was studied using SAXS and cryogenic-TEM. Analysis of the SAXS structure factor indicates that R3F3 interacts with lipid bilayers by ...