DESIGN AND SYNTHESIS OF A PROTEIN BETA-TURN MIMETIC

A nine-membered-ring lactam system (1) has been chosen as a framework for the development of non-peptide molecules to mimic structural features of peptide and protein 8-turns. The synthesis of model di- and tetrapeptide mimetics starting from 1,5-cyclooctadiene derivatives is reported. In the model dipeptide mimetic (9), the amide linkage is trans (NMR, X-ray) and functional groups at positions adjacent to the lactam amide bond correspond closely to the side-chain positions of residues i + 1 and i + 2 of classical type II 8-turns. In the model tetrapeptide mimetic (30), all four side chains of low-energy trans amide conformers of the mimetic are well matched to their peptide counterparts. © 1990, American Chemical Society. All rights reserved.