N-Terminal fatty acylation of peptides spanning the cationic C-terminal segment of bovine β-defensin-2 results in salt-resistant antibacterial activity.

Peptides spanning the C-terminal segment of bovine-β-defensin-2 (BNBD-2) rich in cationic amino acids, show antimicrobial activity. However, they exhibit considerably reduced activity at physiological concentration of NaCl. In the present study, we have investigated whether N-terminal acylation (acetylation and palmitoylation) of these peptides would result in improved antimicrobial activity. N-terminal palmitoylation though increased hydrophobicity of the peptides, did not enhance antimicrobial potency. However, antibacterial activity of these peptides was not attenuated by NaCl. Biophysical studies on the palmitoylated peptides have indicated that antibacterial activity in the presence of NaCl arises due to the ability of the peptides to interact with membranes more effectively. These peptides showed hemolytic activity which was attenuated considerably in the presence of serum and lipid vesicles. In defensin related peptides, fatty acylation would be a convenient way to generate analogs that are active in the presence of salt.