Heterogeneous H-bonding in a foldamer helix.

Structural characterization of new α/γ-peptide foldamers containing the cyclically constrained γ-amino acid I is described. Crystallographic and 2D NMR analysis shows that γ residue I promotes the formation of a 12/10-helical secondary structure in α/γ-peptides. This helix contains two different types of internal H-bond, and the data show that the 12-atom C═O(i) → H-N(i+3) H-bond is more favorable than the 10-atom C═O(i) → H-N(i-1) H-bond. Several foldamer helices featuring topologically distinct H-bonds have been discovered, but our findings are the first to show that such H-bonds may differ in their favorability.