Bactericidal Peptidomimetic Polyurethanes with Remarkable Selectivity against Escherichia coli.

The increasing incidence of drug-resistant strains of bacteria necessitates the development of new classes of antimicrobials. Host defense peptides, also known as antimicrobial peptides, are promising in this regard but have several drawbacks. Herein, we show that peptidomimetic polyurethanes with pendant functional groups that mimic lysine and valine amino acid residues have high antibacterial activity against Gram negative Escherichia coli, yet are less effective against Gram positive Staphylococcus aureus. All the polyurethanes designed in this study display high bactericidal activity against E. coli, whereas the polyurethanes with high concentrations of lysine mimicking functional groups display minimal cytotoxicity toward mammalian cells. Control experiments with pexiganan, an analogue of the host defense peptide magainin, showed that the polyurethanes described here have high bactericidal activity, while having comparable hemocompatibility and lower mammalian cell toxicity. Overall, the results point to an encouraging new class of peptidomimetic synthetic polymers with selective bactericidal activity to E. coli and low mammalian cell toxicity.