Synthesis and antibiotic activity of a gramicidin S analogue containing bicyclic β-turn dipeptides

Abstract

In order to demonstrate the usefulness of a bicyclic dipeptide derivative designed to simulate the backbone conformation of a β-turn (type II′), the dipeptide (3S, 6S, 9R)-2-oxo-3-amino-7-thia-1-azabicyclo[4.3.0]nonane-9-carboxylic acid has been incorporated into gramicidin S (GS) at the β-turns in place of the D-Phe-Pro sequences.The GS analogue exhibited equal antibacterial activity, and a closely similar c.d. spectrum, to that of GS, indicating that there are two β-turns in the biologically active conformation of GS. The method seems applicable to more flexible peptides of biological interest.