Synthesis of acylated gramicidins and the influence of acylation on the interfacial properties and conformational behavior of gramicidin A

Abstract

Five gramicidin A analogs were synthesized in which various acyl chains, differing in length and unsaturation, were covalently coupled to the C-terminal ethanolamine group. The analogs were characterized by various spectroscopic techniques and their molecular properties were investigated using monolayer techniques and circular dichroism. It is demonstrated that neither the interfacial properties nor the conformational behavior of gramicidin A at the air/water interface are seriously affected upon acylation. It is proposed that at the limiting area the gramicidin molecule is oriented with its C-terminus towards the subphase with the covalently coupled acylchain located parallel to the helical axis in between the protruding tryptophans. Circular dichroism experiments, in which gramicidin-containing vesicles were prepared from different organic solvents, indicate that the presence of a covalently coupled fatty acylchain tends to stabilize the beta 6.3 helical conformation. It is demonstrated that, like for gramicidin A, also for the acylgramicidins the single-stranded beta 6.3 helical conformation, or channel conformation, is the preferred conformation upon incorporation in bilayers.