Changes in conformation and antimicrobial properties caused by replacement of D-amino acids with α-aminoisobutyric acid in the gramicidin backbone: synthesis and circular dichroic studies

Abstract

In an attempt to mimic the stable helical structures of proteins with possible pore-forming ability in membranes, the linear gramicidin backbone has been changed by inserting achiral α-aminoisobutyric acids (Aib) in place of all of the alternatively sequenced D-amino acids. The conformation and biological activity of the synthetic gramicidin A and B analogues have been studied. CD measurements have been used to determine the conformation in solution. The original conformation of gramicidin clearly changes and its antimicrobial activity is reduced in Aib analogues. Although α-helical motifs can be clearly distinguished in analogues, the CD spectra show inherent complexities. The possibility of superposition of different conformations is considered. The potential pore-forming ability of analogues is briefly discussed.