Mimicry of antimicrobial peptides with synthetic oligomers and polymers

ORGN 335

Samuel H Gellman, Department of Chemistry, University of Wisconsin, Madison, Madison, WI 53706
Among the strategies employed by multicellular organisms to fight off bacterial infection is the deployment of antimicrobial peptides. These "host-defense" peptides generally display broad-spectrum activity against bacteria, and their toxicity toward eukaryotic cells is low. The host-defense peptides come in a variety of sizes and shapes. Among the best studied are those that can adopt a globally amphiphilic alpha-helical conformation, i.e., a helix that has cationic side chains segregated along one side and hydrophobic residues segregated along the other. Our laboratory showed a few years ago that the antimicrobial activity of helical host-defense peptides could be mimicked with unnatural oligomers that adopt globally amphiphilic helical conformations. More recently we have begun to study amphiphilic polymers for the ability to mimic host-defense peptides. Such polymers are chemically heterogeneous, unlike peptides or synthetic oligomers prepared via step-wise synthesis. However, polymerization is a much less expensive mode of preparation than is step-wise synthesis.