Biomimetic Facially Amphiphilic Antibacterial Oligomers with Conformationally Stiff Backbones

SummaryA foldamer has been designed with a conformationally stiff backbone that is facially amphiphilic. The oligomer has excellent antimicrobial activity and was found to be 18 times more active toward bacterial cells than human red blood cells. The oligomer is built from arylamide bonds around a central 4,6-dicarboxy pyrimidine ring. The conformation was studied by X-ray crystallography and solution NMR spectroscopy. Density-functional (DFT) calculations were performed to guide the design. These calculations accurately predicted the overall conformation as well as NMR chemical shifts. Antibacterial activity was demonstrated against E. coli, a gram-negative strain, and B. subtilis, a gram-positive strain. The minimal inhibitory concentration is 0.8 μg/ml.