Hybrid analogues of gramicidin S and gratisin.

tions with C2 symmetry and results in disruption of its cell membrane.1-9,13) In addition, no resistance has been found for the antibiotics, because it requires significant alteration of the lipid composition of the cell membrane.14) In view of the fact that widespread antibiotic resistance has become a serious threat to public health15-18), these amphiphilic antibiotics are attractive targets for new drug discovery. In these studies, we would like to report the design and synthesis of a new hybrid analogue, cyclo (-Val-Orn-Leu-DPhe-Pro-Val-Orn-Leu-D-Phe-Pro-D-Tyr-) (7a), containing both the sequences of the (GS) pentapeptide (-Val-OrnLeu-D-Phe-Pro-) and the (GR) hexapeptide (-Val-Orn-LeuD-Phe-Pro-D-Tyr-) in the molecule (Fig. 1). The antiparallel