Design, synthesis and characterization of antimicrobial pseudopeptides corresponding to membrane-active peptide.

To obtain active and metabolically stable analogues, peptide backbone modifications have been incorporated into many biologically active peptides. In this study, we designed and synthesized pseudopeptides corresponding to the antimicrobial peptide that acted on the lipid membrane of the pathogen. Most pseudopeptides exhibited a longer half-life than the peptide in the presence of serum as well as a considerable activity against test bacteria and fungi. Circular dichroism spectra and retention times of the pseudopeptides helped us to elucidate the effect of the incorporation of backbone modifications on the structural parameters necessary for the activity, indicating that alpha-helical structure was the most important factor for the activity and hydrophobicity had a considerable effect on the activity. Backbone modifications employed in this study can be a useful tool for structure-activity relationship studies and the development of therapeutic agents from membrane-active antimicrobial peptides.