Optimization of the antimicrobial activity of magainin peptides by modification of charge

FEBS Lett. 2001 Jul 20;501(2-3):146-50. doi: 10.1016/s0014-5793(01)02648-5.


Investigation of magainin II amide analogs with cationic charges ranging between +3 and +7 showed that enhancement of the peptide charge up to a threshold value of +5 and conservation of appropriate hydrophobic properties optimized the antimicrobial activity and selectivity. High selectivity was the result of both enhanced antimicrobial and reduced hemolytic activity. Charge increase beyond +5 with retention of other structural motifs led to a dramatic increase of hemolytic activity and loss of antimicrobial selectivity. Selectivity could be restored by reduction of the hydrophobicity of the hydrophobic helix surface (H(hd)), a structural parameter not previously considered to modulate activity. Dye release experiments with lipid vesicles revealed that the potential of peptide charge to modulate membrane activity is limited: on highly negatively charged 1-palmitoyl-2-oleoylphosphatidyl-DL-glycerol bilayers, reinforcement of electrostatic interactions had an activity-reducing effect. On neutral 1-palmitoyl-2-oleoylphosphatidylcholine bilayers, the high activity was determined by H(hd). H(hd) values above a certain threshold led to effective permeabilization of all lipid systems and even compensated for the activity-reducing effect of charge increase on highly negatively charged membranes.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Binding Sites
  • Escherichia coli / drug effects
  • Hemolysis / drug effects*
  • Humans
  • Magainins
  • Microbial Sensitivity Tests
  • Peptides / chemistry
  • Peptides / pharmacology
  • Permeability / drug effects
  • Protein Conformation
  • Xenopus Proteins*


  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Magainins
  • Peptides
  • Xenopus Proteins
  • magainin 2 peptide, Xenopus