Mimicking ß-sheet assembly in aqueous media: Progress towards the controlled dimerization of peptidic macrocycles

ORGN 569

Gregory A. Watkins and Paul A. Bartlett. Department of Chemistry, University of California - Berkeley, Box 112 PAB Research Group, University of California, Berkeley, CA 94720-1460
We have synthesized a number of rigid, C2-symmetric macrocycles, designed to self-assemble in aqueous media to form soluble, four-stranded ß-sheets. A representative target molecule contains two amphipathic peptide strands--representing the i and (i + 3) strands of a naturally occurring ß-sheet--capped by two rigid, computationally-designed templates. Such molecules may be rapidly synthesized via a bimolecular cyclization stragegy. We anticipate each subunit of this type to generate a pair of diastereomeric, antiparallel ß-sheets under neutral, aqueous conditions. Characterization of this process is underway, using techniques including circular dichroism, NMR, and fluorescence quenching experiments.