STRUCTURE AND FUNCTION IN BETA-PEPTIDE FOLDAMERS

Sam Gellman
Department of Chemistry
University of Wisconsin, Madison



Proteins perform a wide range of complex chemical functions in biological systems. Nearly all of these molecular operations require the polypeptide chain to adopt a compact and specific folding pattern. We are trying to induce analogous folding behavior in unnatural oligomers ("foldamers"), with the long-range goal of generating protein-like functions.

Our efforts have focused on b-amino acid oligomers ("b-peptides"). We have found that all three types of secondary structure observed in folded proteins, helix, sheet and turn, are displayed by b-peptides in organic solvents, when properly selected residues are employed.

We have been able to generate b-peptide secondary structures that are very stable in aqueous solution. Amphiphilic b-peptides that adopt helical conformations in aqueous solution display potent antimicrobial activity; these b-peptides are mimics of host-defense peptides like magainins.