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.
Kang
Su-Jin
SJ
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Won
Hyung-Sik
HS
Choi
Wahn-Soo
WS
Lee
Bong-Jin
BJ
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002942:Circular Dichroism; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry*
D023181:Antimicrobial Cationic Peptides; D014364:Tryptophan