Effects of net charge and the number of positively charged residues on the biological activity of amphipathic a-helical cationic antimicrobial peptides

摘要

The widespread use of classical antibiotics has resulted in the emergence of many antibiotic-resistant strains. Cationic antimicrobial peptides (AMPs) have become important candidates as potential therapeutic agents. Cationic AMPs of the a-helical class have two unique features: a net positive charge of at least +2 and an amphipathic character, with a non-polar face and a polar/charged face.We previously designed a peptide VI3K from our original a-helical antimicrobial peptide V681, which had excellent antimicrobial activity but also exhibited high toxicity [1]. D-V13K showed greater antimicrobial activity, no toxicity and excellent stability to proteolytic digestion compared to D-V681. The valine to lysine substitution in the center of the non-polar face is the first report of a specificity determinant in a-helical antimicrobial peptides between eukaryotic and prokaryotic cells. The hydrophobic residues on the non-polar face of the helix played a more important role in stabilizing peptide secondary structure than residues on the polar face and are an essential requirement for antimicrobial activity.