Membrane interactions of antimicrobial beta-peptides: the role of amphipathicity versus secondary structure induction.

The membrane interaction of two beta peptides was studied using a surface plasmon resonance biosensor. The two peptides are beta-17, a novel beta-amino acid based antimicrobial peptide and the corresponding scrambled-beta17--a non-antimicrobial beta-peptide analogue. Membrane interaction studies were performed with a series of phospholipid mixtures which mimic either mammalian cells (high in phosphatidylcholine and cholesterol) or microbial cells (high in phosphatidylethanolamine and phosphatidylglycerol). The results were compared with the membrane binding of the well-characterized antimicrobial peptide magainin 2. The secondary structure of these peptides were also determined in each lipid mixture by circular dichroism and correlated with the membrane-binding properties. Both beta-17 and the scrambled peptide have the same peptide length, charge and showed a similar secondary structure in both aqueous buffer and in the presence of liposomes. Both peptides also bound to a similar level on each membrane mixture, showing that the dramatic difference in biological activity is not based on the amount of peptide bound but rather differences in the degree of insertion and rate of membrane dissociation. Although beta-17 and the scrambled beta-17 peptide exhibited similar binding properties on all membrane mimics, both beta-peptides bound more to all membranes compared with magainin 2. Overall, the results further reveal the significant interplay between peptide amphipathicity and secondary structure induction on membrane binding.