Stabilization of Azapeptides by Namide···H–Namide Hydrogen Bonds

Abstract

An unusual Namide···H–Namide hydrogen bond (HB) was previously proposed to stabilize the azapeptide β-turns. Herein we provide experimental evidence for the Namide···H–Namide HB and show that this HB endows a stabilization of 1–3 kcal·mol–1 and enforces the trans–cis–trans (t–c–t) and cis–cis–trans (c–c–t) amide bond conformations in azapeptides and N-methyl-azapeptides, respectively. Our results indicate that these Namide···H–Namide HBs can have stabilizing contributions even in short azapeptides that cannot fold to form β-turns.