Building a bridge between peptide chemistry and organic chemistry: Intramolecular macrocyclization reactions and supramolecular chemistry with helical peptide substrates

Abstract

In our ongoing efforts to build a bridge between peptide chemistry and organic chemistry, we are currently investigating: (1) two types of intramolecular macrocyclization reactions in 3(10)-helical peptides, and (2) a peptido[2]rotaxane molecular machine as a supramolecular tool using a 3(10)-helical peptide as the axle. More specifically, we studied the following two reactions: (a) the intramolecular ring-closing olefin metathesis between two amino acid residues with side chains bearing an allyl group, and (b) the intramolecular Paternò-Yang photoreaction, using a benzophenone-based amino acid as a photoaffinity reagent for a Met residue. Both reactions involve formation of a new C--C bond. As for the supramolecular system examined, we were able to identify the two stations of a new peptido[2]rotaxane characterized by an -(Aib)(6)- axle and to reversibly switch the aromatic tetramide macrocyclic wheel from one station to the next. This article summarizes the information available in the literature from other groups and the published/unpublished data originated from our laboratory on these research areas.