Effect of Secondary Structure on Biological Activities of Antimicrobial Peptides
A 15-mer cationic α-helical antibacterial peptide was used as the framework to study
the effect of peptide secondary structure on antimicrobial activities. We designed an α-helical
peptide with higher helical propensity compared with the original peptide, a β-sheet peptide and a
random coiled peptide without changing the originalamino acid composition of the peptide
sequence. Three truncated peptides were also designed. The secondary structures of the peptides
were determined by circular dichroism spectra both in aqueous solution and in hydrophobic
environment. The biological activities of the peptides were detected against three Gram-negative
bacterial strains, three Gram-positive bacterial strains and human red blood cells. The results
showed that the two helical peptides exhibited comparable antibacterial activities but their
hemolytic potency (cytotoxicity) varied from extreme hemolysis to no hemolysis, which was
positively correlated with their helical propensity. The β-sheet peptide partially lost both of the
biological activities. The random coiled peptide with the lowest improvement in hemolytic activity
showed comparable antibacterial activity against Gram-positive bacteria but weaker antibacterial
activity against Gram-negative bacteria. Truncated peptides showed inevitable weaker antimicrobial
activity compared to the parent peptide. Our results show that peptide secondary structure is
strongly correlated with hemolytic activity and relatively less correlated with antimicrobial
activity, which provides an insight into the mechanism of action of the antimicrobial peptide