The design and synthesis of a model of protein supersecondary structure : the beta barrel

Abstract

A new synthetic approach to the study of protein structure is presented. I have designed a modular protein sequence which might be expected to fold into a structure resembling a β barrel. The design takes into account many of the factors involved in protein folding such as: hydrophobic interactions, structure nucleating sequences, interior volume requirements, hydrogen bonding preferences and propensities toward intermolecular salt linkage formation. I have designed the structure such that intermediate synthetic products would consist of the structure forming elements of the protein, the β strands and β turns. I have prepared all the peptide components for the formation of two barrels and have shown that one of the major components of one barrel has the predicted structure even though it was not incorporated into a completed peptide. Several of the octapeptides ("β strands") were shown to be capable of being coupled to the minor fragments ("β turns") by model reactions utilizing precursors of the major fragments. This demonstrates the synthetic feasibility of our approach to a novel method for the study of protein structure, the synthesis of a basic building block of proteins: the β barrel.