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.

Autor: Lin Q; Department of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK., Lan H; School of Chemistry, University of Bristol, Cantocks Close, Bristol, BS8 1TS, UK., Ma C; School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China., Stendall RT; Department of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK., Shankland K; School of Chemistry, Food and Pharmacy (SCFP), University of Reading, Whiteknights Berks, Reading, RG6 6AD, UK., Musgrave RA; Department of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK., Horton PN; EPSRC National Crystallography Service, School of Chemistry, University of Southampton Highfield, Southampton, SO17 1BJ, UK., Baldauf C; Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, 14195, Berlin, Germany., Hofmann HJ; Institut für Biochemie, Universität Leipzig, Brüderstrasse 34, 04103, Leipzig, Germany., Butts CP; School of Chemistry, University of Bristol, Cantocks Close, Bristol, BS8 1TS, UK., Müller MM; Department of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK., Cobb AJA; Department of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 Sep 04; Vol. 62 (36), pp. e202305326. Date of Electronic Publication: 2023 Jun 14.
DOI: 10.1002/anie.202305326
Abstrakt: 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.
(© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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