Structural features of helical antimicrobial peptides: their potential to modulate activity on model membranes and biological cells.

Antibacterial, membrane-lytic peptides belong to the innate immune system and host defense mechanism of a multitude of animals and plants. The largest group of peptide antibiotics comprises peptides which fold into an amphipathic alpha-helical conformation when interacting with the target. The activity of these peptides is thought to be determined by global structural parameters rather than by the specific amino acid sequence. This review is concerned with the influence of structural parameters, such as peptide helicity, hydrophobicity, hydrophobic moment, peptide charge and the size of the hydrophobic/hydrophilic domain, on membrane activity and selectivity. The potential of these parameters to increase the antibacterial activity and to improve the prokaryotic selectivity of natural and model peptides is assessed. Furthermore, biophysical studies are summarized which elucidated the molecular basis for activity and selectivity modulations on the level of model membranes. Finally, the knowledge about the role of peptide structural parameters is applied to understand the different activity spectra of natural membrane-lytic peptides.