1.D.25 The Arylamine Foldamer (AAF) Family
Small arylamide foldamers, designed to mimic the amphiphilic nature of antimicrobial peptides, are bactericidal against both Gram-negative and Gram-positive bacteria (Mensa et al., 2011). These foldamers cause large changes in the permeability of the outer-membrane of Escherichia coli and more limited permeabilization of the inner membrane which reaches critical levels corresponding with the time required to bring about bacterial cell death. Transcriptional profiling of E. coli treated with sub-lethal concentrations of the arylamides showed induction of genes related to membrane and oxidative stresses, with some overlap to the effects observed for polymyxin B (Mensa et al., 2011). Protein secretion into the periplasm and the outer-membrane is also compromised, possibly contributing to the lethality of the arylamide compounds.