The increasing prevalence of antibiotic drug resistant bacteria (superbugs) have threatened to undo a century of medical advances. As opposed to target specific conventional antibiotics, the development of bacterial resistance toward cationic natural host defense antimicrobial peptides (AMPs) is believed to be improbable due to the ability of AMPs to non-specifically target and rupture the bacterial cell surface.1 Synthetic amphiphilic polymers, mimicking the design features of AMPs, have emerged as promising candidates to combat superbug infections, owing to their facile synthesis and structural tunability. However, the toxicity of synthetic amphiphilic polymers toward mammalian cells have impeded their therapeutic applications. We investigated the control of spacer arm (distance from the polymer backbone to cationic center) lengths and copolymer composition on the biological activities of synthetic amphiphilic polymers.2 Our strategy of controlling the charge distribution and counit ratios by copolymerizing a 6-carbon spacer arm monomer with a 2-carbon spacer arm monomer resulted in a polymer with more than 200 fold selectivity toward gram negative Escherichia coli over red blood cells (RBCs). Moreover, these polymer displayed as high as 100 times selective activity against gram positive Staphylococcus aureus over RBCs. Scanning electron microscopy analysis and time-dependent killing efficiency studies confirmed the membrane disruption bactericidal activity of our polymers. References 1. Zasloff, M., Nature 2002, 415, 389-395. 2. Punia, A; He, E.; Lee, K.; Banerjee, P.; Yang, N., Chem. Commun. 2014, 50, 7071-7074.

Control of spacer arm strategy to synthesize amphiphilic polymers with highly selective bactericidal activity

249th National Meeting (2015)

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