Synthesis of [hexafluorovalyl(1,1')]gramicidin S

[Hexafluorovalyl(1,1')]gramicidin S (8), in which two valine residues in the natural gramicidin 8 were replaced by L-hexafluorovaline (Hfv) residues, was synthesized by the solid-phase-synthesis and cyclization-cleavage method on benzophenone oxime resin. Though the racemic hexafluorovaline derivative was employed for the peptide synthesis, the desired product was isolated in moderate yield, probably reflecting the stable cyclic structure of 8. CD and (1)HNMR spectra indicated that the conformation of 8 is similar to that of gramicidin 8. The two beta-turn structure and antiparallel beta-sheet structure with four intramolecular hydrogen bondings were maintained in spite of introducing the hexafluorovaline residues. The dye-release experiment from lecithin vesicle and antimacrobial activity assay also indicated that 8 showed membrane-disturbing activity like gramicidin 8, although the activity of 8 was somewhat weaker than gramicidin 8.