SYNTHESIS OF [L-ALPHA-AMINOMYRISTIC ACID3,3']GRAMICIDIN-S AND ITS INTERACTION WITH PHOSPHOLIPID-BILAYER

A lipophilized gramicidin S (GS) analog was synthesized by introducing L-alpha-aminomyristic acid (Amy) residues instead of L-leucine residues by the conventional solution method. Influences of lipophilization of GS on interaction with phospholipid liposomes were examined by the peptide-induced dye-leakage assays using carboxyfluorescein (CF)-entrapped liposomes of dipalmitoyl-DL-alpha-phosphatidylcholine (DPPC). The [Amy3,3']GS (Amy-GS) had the enhanced ability of CF-leakage below the phase-transition temperature of DPPC liposomes as compared with GS, while it showed weaker leakage ability at higher temperature. Conformation of Amy-GS in solution and in the presence of liposomes was similar to that of GS, which was elucidated by CD and H-1 NMR measurements. The Amy residue can be utilized to enhance the affinity of a peptide to membrane environment without changing conformation of an original peptide.