Effects of the phosphatidylglycerol head group on the binding of short dermcidin-derived peptides to the phospholipid membrane surface

Dermcidin (DCD) is a human peptide composed of 110 amino acids. When secreted into sweat, DCD undergoes postsecretory proteolytic processing to give the short antimicrobial peptides SSL-23 and SSL-25. As an initial phase of studies directed toward understanding the structural basis of the biological functions of these peptides, we chemically synthesized naturally occurring SSL-23 and SSL-25, as well as the artificial sequences SSL-21 and SSL-27, and analyzed their molecular interaction with bacterial and mammalian model surfaces. While dynamic-coating HPLC and CD spectroscopy revealed that the four SSL peptides selectively bound to a bacterial model membrane containing 1,2-dimyristoyl phosphatidylglycerol (DMPG) and underwent large structural changes, 31P NMR studies of the liposomes suggested that the attractive interaction between the peptides and DMPG did not lead to ion-pore formation or disruption of the model membrane. Our results strongly indicate that the SSL peptides express their selectivity to microorganisms by recognizing the head groups of their cell surface lipid.