Influence of the hydrophobic amino acids in the N- and C-terminal regions of pleurocidin on antifungal activity.

To investigate the influence of N- or C-terminal regions of pleurocidin (Ple) peptide on the antifungal activity, four analogues partially truncated in the N- or C-terminal regions were designed and synthesized. Circular dichroism (CD) spectroscopy demonstrated that all the analogues maintained an alpha-helical structure. The antifungal susceptibility testing also showed that the analogues exhibited antifungal activities against human fungal pathogens, without hemolytic effects against human erythrocytes. The result further indicated that the analogues had discrepant antifungal activities (Ple > Ple (1-22) > Ple (4-25) > Ple (1-19) > Ple (7-25)) and that N-terminal deletion affected the activities much more than C-terminal deletion. Hydrophobicity (Ple > Ple (1-22) > Ple (4-25) > Ple (1-19) > Ple (7-25)) was thought to have been one of the consistent factors that influenced these activity patterns, rather than the other primary factors like the helicity (Ple > Ple (4-25) > Ple (1-22) > Ple (1-19) > Ple (7-25)) or the net charge (Ple = Ple (4-25) = Ple (7-25) > Ple (1-22) = Ple (1-19)) of the peptides. Taken together, the hydrophobic amino acids in the N-terminal region of Ple is more crucial for the antifungal activity than those in the C-terminal region.