Mammalian cell toxicity and candidacidal mechanism of Arg- or Lys-containing Trp-rich model antimicrobial peptides and their d-enantiomeric peptides

▶ Arg-containing peptides (R6L2W3 and R6L2W3-d) were more toxic to human erythrocytes and mammalian cells as compared to Lys-containing peptides (K6L2W3 and K6L2W3-d). ▶ Arg-containing peptides are slightly more hydrophobic than Lys-containing peptides. ▶ A little difference in the hydrophobicity of peptides affect their hemolytic activity and mammalian cell toxicity. ▶ Lys-containing peptides penetrated the cell wall and cell membrane and accumulated inside the cells, whereas Arg-containing peptides did not penetrate but associated with the membranes. ▶ The ultimate target site of action of Arg-containing peptides and Lys-containing peptides may be the membrane and the cytoplasm of Candida albicans, respectively.