Stabilization of Azapeptides by Namide•••H-Namide Hydrogen Bonds

An unusual N-amide center dot center dot center dot H-Namide hydrogen bond (HB) was previously proposed to stabilize the azapeptide beta-turns. Herein we provide experimental evidence for the N-amide center dot center dot center dot 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 N-amide center dot center dot center dot H-Namide HBs can have stabilizing contributions even in short azapeptides that cannot fold to form beta-turns.

Automated summary

Experimental evidence has confirmed the presence of N-amide···H-Namide hydrogen bonds in azapeptides, which provide stabilization effects. These hydrogen bonds enforce specific amide bond conformations in azapeptides and N-methyl-azapeptides.