Dimerization of the antimicrobial peptide arenicin plays a key role in the cytotoxicity but not in the antibacterial activity.

The β-hairpin antimicrobial peptides arenicins from marine polychaeta Arenicola marina exhibit a broad spectrum of antimicrobial activity and high cytotoxicity. In this study the biological activities of arenicin-1 and its therapeutically valuable analog Ar-1[V8R] were investigated. The peptide Ar-1[V8R] displays significantly reduced cytotoxicity against mammalian cells relative to the wild-type arenicin-1. At the same time, both peptides exhibit similar antibacterial activities and kinetics of bacterial membrane permeabilization. Comparative NMR analysis of the peptides spatial structures in water and membrane-mimicking environment showed that Ar-1[V8R] in contrast to arenicin has significantly lower dimerization propensity. Thus, dimerization of the antimicrobial peptide arenicin plays a key role in the cytotoxicity but not in the antibacterial activity.