The foci of this research are twofold. First, the development of new independently folded polypeptide motifs will be carried out. The two design targets are an all beta-structure (BBB) motif and a mixed alpha- and beta- structure patterned after charybotoxin which includes a number of disulfides in the native state. Second, the structure of the BBA motif will be manipulated to effect the formation of a discrete dimeric structure by `domain swapping.` A key feature of the dimerization studies will be the development of fluorescent amino acids with solvatochromic properties for studying protein association phenomena. With this renewal award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Barbara Imperiali of the Division of Chemistry at the California Institute of Technology. Professor Imperiali will focus her work on designing and developing methods for the de novo synthesis of functional polypeptides. The detailed analysis of the cooperative forces involved in folding small oligopeptides into compact structures will contribute to the understanding of the architecture of the protein biopolymer.
