Syntheses of low-hemolytic antimicrobial gratisin peptides

Antibiotic and hemolytic activities of gratisin (GR), cyclo(-Val1-Orn2-Leu3-d-Phe4-Pro5-d-Tyr6-)2, and fifteen GR analogues, which have various d-amino acid residues in place of d-Tyr6,6′ residues, were examined. Among them, [d-Orn6,6′]-GR, [d-Lys6,6′]-GR and [d-Arg6,6′]-GR showed the strong activity against both Gram-positive and Gram-negative bacteria. In addition, the antibiotics showed significantly reduced toxicity against human blood cells compared with gramicidin S, cyclo(-Val1-Orn2-Leu3-d-Phe4-Pro5-)2.