THE DESIGN AND CONSTRUCTION OF SYNTHETIC PROTEIN MIMICS

A strategy for the modular construction of synthetic protein mimics based on the ability of non-protein amino acids to act as stereochemical directors of polypeptide chain folding, is described. The use of alpha-aminoisobutyric acid (Aib) to construct stereochemically rigid helices is exemplified by crystallographic and spectroscopic studies of several apolar peptides, ranging in length from seven to sixteen residues. The problem of linker design in elaborating alpha, alpha-motifs is considered. Analysis of protein crystal structure data provides a guide to choosing linking sequences. Attempts at constructing linked helical Motifs using linking Gly-Pro segments are described. Ths use of flexible linkers, like epsilon-aminocaproic acid is examined and the crystallographic and solution state analysis of a linked helix motif is presented. The use of bulky sidechain modifications on a helical scaffold, as a means of generating putative binding sites is exemplified by a crystal structure ot a peptide packed in a parallel zipper arrangement.