We report the first NMR and X-ray diffraction (XRD) structures of an unusual 13/11-helix (alternating i, i+1 {NH-O=C} and i, i+3 {C=O-H-N} H-bonds) formed by a heteromeric 1 : 1 sequence of α- and δ-amino acids, and demonstrate the application of this framework towards catalysis. Whilst intramolecular hydrogen bonds (IMHBs) are the clear driver of helix formation in this system, we also observe an apolar interaction between the ethyl residue of one δ-amino acid and the cyclohexyl group of the next δ-residue in the sequence that seems to stabilize one type of helix over another. To the best of our knowledge this type of additional stabilization leading to a specific helical preference has not been observed before. Critically, the helix type realized places the α-residue functionalities in positions proximal enough to engage in bifunctional catalysis as demonstrated in the application of our system as a minimalist aldolase mimic.
A new catalytic foldamer constructed of α‐ and bespoke δ‐residues forms a helix which is not only stabilized by intramolecular H‐bonds, but also by apolar interactions not observed in foldamer secondary structures until now. The resulting scaffold gives a useful juxtaposition of functionality and leads to bifunctional catalysis as demonstrated through an aldolase‐like process.
Keywords: aldolase; catalysis; helical conformation; peptides; peptidic foldamers.
© 2023 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.