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

Wei Sheng Wu Xue Bao. 2011 Mar;51(3):346-51.

Abstract

Objective: The amphipathic alpha-helical peptide is an important class of antimicrobial peptides. In this study, a 16-residue-long peptide (VGR16) composed of 8 Val residues in the nonpolar face and 5 Arg residues in the polar face was 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 16 microg/ml to 64 microg/ml. VGR16 also exhibited rapid bactericidal action. It was surprisingly found that the peptide displayed no hemolytic activity even at a concentration of 256 microg/ml. Cell culture assays indicated that the peptide VGR16 had low cytotoxicity against mammalian cells.

Conclusion: The results showed that the peptide could be a likely candidate for future antimicrobial applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Arginine / chemistry*
  • Drug Design
  • Microbial Sensitivity Tests / methods
  • Peptides / chemistry*
  • Peptides / pharmacology*
  • Protein Structure, Secondary
  • Structure-Activity Relationship
  • Valine / chemistry*

Substances

  • Anti-Bacterial Agents
  • Peptides
  • Arginine
  • Valine