Deformylated Gramicidin A and Its Derivatives Showing High Antimicrobial Activity and Low Hemolytic Toxicity

Gramicidin A is a natural peptide, which shows high antimicrobial activity to Gram-positive bacteria. However, the hemolytic toxicity prevents its therapeutic usage. We demonstrated that by simply removing the formyl group at the N terminus, the hemolytic toxicity of the peptide could be obviously decreased. The deformylated gramicidin A (1) could efficiently insert into the lipid bilayer to form transmembrane channels. The peptide can also selectively insert into the membrane of Gram-positive bacteria but not that of erythrocytes, leading to its high antimicrobial activity and very low hemolytic toxicity. The derivation of 1 could be achieved by decoration at the terminal NH₂ group, which also produced peptides showing high activity and low hemolytic toxicity. This derivation method provided us with an efficient strategy to build a library for future activity and cytotoxicity screening in vitro and in vivo.