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

Summary of main observation and conclusion 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 NH 2 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 .