Rational design of α-helical antimicrobial peptide with Val and Arg residues

Abstract:

Abstract: [Objective] The amphipathic α-helical peptide is an important class of antimicrobial peptides. In this study, 16-residue-long peptide (VGR16) composed of 8 Val residues in the nonpolar face and 5 Arg residues in the polar face were designed based on the helical wheel projection to produce antimicrobial peptide with improved antibacterial activity accompanied by decreased toxicity. [Methods] Antimicrobial activity and toxicity against red blood cells and mammalian cells were investigated to evaluate the biological function of the peptide. In addition, bactericidal kinetics was tested. [Results] Antimicrobial assays revealed that the peptide VGR16 showed antimicrobial activity and their MICs against gram-negative and gram-positive bacteria ranged from 16μg/ml to 64μg/ml, respectively. VGR16 also exhibited rapid bactericidal action. It was surprisingly found that the peptide displayed no hemolytic activity even at a concentration of 256 μg/ml. Cell culture assays indicated that the peptide VGR16 had no cytotoxicity against mammalian cells for its MICs. [Conclusion] The results showed that the peptide could be a likely candidate for future antimicrobial applications.

Key words:Keywords: antimicrobial peptides, α-helical, residues, hemolysis, cytotoxicity