Polycationic Gramicidin S Analogues with Both High Antibiotic Activity and Very Low Hemolytic Activity

The substitution of each constituent amino acid residue of gramicidin S (GS), cyclo(-Val1,1′-Orn2,2′-Leu3,3′-D-Phe4,4′-Pro5,5′-)2 with Lys residue indicated that each side chain structure of the constituent amino acid residues affect largely the antibiotic activity and hemolytic activity of GS. Further, the substitution of D-Phe4,4′ and Pro5,5′ residues with basic amino acid residues as a Lys residue results the high antibiotic activity and the very low hemolytic activity. Thus, we have found novel positions on the scaffold of GS at D-Phe4,4′ and Pro5,5′ residues whose modification will significantly increase the therapeutic index.