β,γ-diamino acids as building blocks for new analogues of Gramicidin S: Synthesis and biological activity

Abstract

We describe here the synthesis and biological activity study of a pair of diastereomeric analogues of Gramicidin S using β,γ-diamino acids as β-turn mimic. The synthesis of the orthogonally protected β,γ-diamino acids was achieved in 6 steps starting from d-alanine. The analogues were then synthesized in solution phase and on solid phase. Biological activity tests showed that, compared with Gramicidin S, both analogues exerted diminished hemolytic activity while they retained interesting antibacterial activity.

Keywords: Antimicrobial peptides; Gramicidin S analogues; Hemolytic activity; β,γ-diamino acids.