Antimicrobially active cycloundecapeptides related to gramicidin S having a novel turn structure with cis D-Phe-Pro peptide bond.

Antimicrobially active cycloundecapeptides related to gramicidin S, cyclo(-Val1-Orn2-Leu3-X4-D-Phe5-Pro6-Val7-Orn8- Leu9-D-Phe10-Pro11-) (X= Leu (1), Ala (2), Orn (3), Lys (4) and Arg (5)), were synthesized. From the CD and NMR studies, 1-5 possess antiparallel -sheet conformation linked by a type II -turn around D-Phe10-Pro11 and a novel turn structure around X4-D-Phe5-Pro6 sequence with cis D-Phe-Pro peptide bond. The structural modifications at position 4 of 1-5 are beneficial to identification of novel antibiotic candidates without hemolytic activity.

Syntheses of low-hemolytic antimicrobial gratisin peptides.

Antibiotic and hemolytic activities of gratisin (GR), cyclo(-Val(1)-Orn(2)-Leu(3)-d-Phe(4)-Pro(5)-d-Tyr(6)-)(2), and fifteen GR analogues, which have various d-amino acid residues in place of d-Tyr(6,6') residues, were examined. Among them, [d-Orn(6,6')]-GR, [d-Lys(6,6')]-GR and [d-Arg(6,6')]-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(-Val(1)-Orn(2)-Leu(3)-d-Phe(4)-Pro(5)-)(2).

A novel polycationic analogue of gratisin with antibiotic activity against both Gram-positive and Gram-negative bacteria.

A novel polycationic analogue of gratisin, cyclo(-Val-Orn-Leu-D-Phe-Pro-D-Lys-)2, was designed and synthesized, which exhibited strong activity against all Gram-positive and Gram-negative bacteria tested. Its activity against Pseudomonas aeruginosa IFO 3080 was two times higher than gramicidin S.