The effect of charge increase on the specificity and activity of a short antimicrobial peptide.

By using short linear antimicrobial peptides as a model system, the effect of peptide charge on the specificity between Candida albicans (fungi) and Gram-positive bacteria was investigated. In a present study, we added and/or deleted lysine residue(s) at the C-terminal and/or N-terminal end(s) of an antimicrobial peptide (KKVVFKVKFK-NH(2)) and synthesized the peptides that had similar alpha helical structures in a lipid membrane mimic condition. The increase of peptide charge improved antifungal activity without the change of antibacterial activity. Structure-activity relationship study about the peptides revealed that the net positive charge must play an important role in the specificity between C. albicans and Gram-positive bacteria and the increase of the net positive charge without the moderate change of secondary structure could improve activity for C. albicans rather than Gram-positive bacteria.