Amphiphilic Polymers with Potent Antibacterial Activity

Abstract

A general strategy is summarized for the assembly of polar and nonpolar domains into a modular monomer structure. Living ring-opening metathesis polymerization (ROMP) of these monomers provides access to a large range of molecular weights with narrow molecular weight distributions. The character and size of each domain can be tuned independently and locked into the repeating unit of the amphiphilic polymers. Lipid membrane disruption activities were investigated for amphiphilic polynorbomene derivatives against liposomes. Water-soluble, amphiphilic, cationic polynorbomene derivatives, which exhibited the highest level of activities against liposome membranes, were then probed for their antibacterial activities in growth inhibition assays and hemolytic activities against human red blood cells in order to determine the selectivity of the polymers for bacterial over mammalian cells. By tuning the overall hydrophobicity of the polymer, highly selective, non-hemolytic antibacterial activities were obtained. These simple polymers represent a new approach to the development of nontoxic, broad-spectrum antimicrobials and have significant potential for applications in bio-terrorism defense.