The sharp increase of microbial resistance against antibiotics is a global health threat, which have induced intensive research on antimicrobial agents. As persistent cells often become slow-growing or dormant, strategies targeting their membrane are becoming more relevant. In this respect, artificial assemblies of compounds with membrane activity and antimicrobial potential are thus highly interesting as potential new set of antibiotic agents. Considering that natural peptides with membrane activity are present in the innate immune system without resistance developed against them, these are interesting for development of novel antimicrobial compounds. Note, however, that bioavailability of these compounds is limited due to their sensitivity against degrading enzymes. Consequently, in recent decades an exponentially growing scientific interest is observed for peptidomimetic foldamers, which are peptide-based artificial compounds with structural diversity and folding properties often matching those of natural peptides. The membrane properties of these compounds however, is still poorly understood, therefore in the present proposal I aimed to develop and investigate non-natural foldamers that are capable of interacting with the lipid bilayer. Under the project period we have developed foldamers which readily interact with model membranes but at the same time are water soluble. Biophysical measurements also indicate, that these compounds oligomerize into preferentially beta-sheet rich assemblies, but do not form infinite fibrils. Based on these results we hope that this construct can be used in the future to develop novel non-natural species with antimicrobial potential.
