Crystal structure and NMR of an α,δ‐peptide foldamer helix shows side-chains are well placed for bifunctional catalysis : application as a minimalist aldolase mimic

Lin, Q., Lan, H., Ma, C., Stendall, R. T., Shankland, K. ORCID: https://orcid.org/0000-0001-6566-0155, Musgrave, R. A., Horton, P. N., Baldaug, C., Hofmann, H.-J., Butts, C. P., Müller, M. M. and Cobb, A. J. A. (2023) Crystal structure and NMR of an α,δ‐peptide foldamer helix shows side-chains are well placed for bifunctional catalysis : application as a minimalist aldolase mimic. Angewandte Chemie International Edition, 62 (36). e202305326. ISSN 1433-7851 doi: 10.1002/anie.202305326

Abstract/Summary

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 alpha- and delta-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 delta-amino acid and the cyclohexyl group of the next delta-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 a-residue functionalities in positions proximal enough to engage in bifunctional catalysis as demonstrated in the application of our system as a minimalist aldolase mimic.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/112043
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > Xray (CAF) Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
Publisher	John Wiley & Sons
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