Synthetic peptides corresponding to the beta-hairpin loop of rabbit defensin NP-2 show antimicrobial activity.

Mammalian defensins, a class of antibacterial peptides, are composed of 29-35 amino acids with six cysteines which form three disulfide bonds. Structural studies indicate a triple stranded beta-sheet structure with a well defined beta-hairpin loop at the C-terminal region. It is demonstrated in this report that 18 and 26 residue synthetic peptides corresponding to the beta-hairpin region, constrained by a single disulfide bond, have potent antimicrobial activity without hemolytic activity. Circular dichroism spectroscopy indicates that the single S-S bridge appears to constrain the peptides to a beta-structure. Peptides corresponding to the beta-hairpin region of defensins could thus be attractive candidates as therapeutic agents as well as good model compounds for investigation of the various physiological actions of defensins. Copyright 1999 Academic Press.