Rationally designed bicyclic lactams control different turn motifs and folding patterns in hexapeptide mimics

Conformational analysis of N-acetylated hexapeptide mimics incorporating a bicyclic lactam (1-4) was carried out by a combination of H-1-NMR spectrosc opy, IR spectroscopy, and computer modeling. The nature of the bicyclic lac tam determines the turn motifs and the folding patterns of these constraine d peptides. The (5,6)-bicyclic lactam derivatives 1 and 2, characterized by a type-II' beta-turn (C=O-3... H-6-N), are very compact intramolecularly H -bonded structures. The (5,7)-bicyclic lactam derivative 3, characterized b y an inverse gamma-turn (C=O-4... H-6-N), is a quite flexible "tweezer-like " structure.