De novo generation of antimicrobial LK peptides with a single tryptophan at the critical amphipathic interface.

De novo design of amphipathic model peptides has been successful for generating many antimicrobial peptides with various lengths and amino acid compositions. Here, we suggest a very simple strategy to design antimicrobial peptides with a short length and a simple amino acid composition. Amphipathic helical properties were conferred by using only leucines and lysines and a single tryptophan was positioned at the critical amphipathic interface between the hydrophilic ending side and the hydrophobic starting side, in the helical wheel projection. According to this rule, the model peptides with 7 to 13 residues exhibited antimicrobial activity. Among them, the most potent activity against both Gram-positive and Gram-negative bacteria, covering all of the nine bacterial strains tested in this study, was found for the 11-mer sequences having a 1:1 (L(5)K(5)W(6)) or a 3:2 (L(6)K(4)W(6)) ratio of leucines to lysines. In particular, the former peptide L(5)K(5)W(6) could be evaluated as the most useful agent, as it showed no significant hemolytic activity with a broad-spectrum of antimicrobial activity.