@article{7d255b8c8a58456ea11698b4e19321dd,
title = "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",
abstract = "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.",
author = "Qi Lin and Hao Lan and Chunmiao Ma and Stendall, {Ryan T} and Kenneth Shankland and Musgrave, {Rebecca A} and Horton, {Peter N} and Carsten Baldauf and Hans-J{\"o}rg Hofmann and Butts, {Craig P} and M{\"u}ller, {Manuel M} and Cobb, {Alexander J A}",
note = "Funding Information: We thank The Leverhulme Trust for funding from a Research Project Grant (RPG‐2019‐283), in addition to King's College London and the China Scholarship Council (Studentship to QL) as well as the Wellcome Trust and the Royal Society (Sir Henry Dale Fellowship to MM, 202250/Z/16/Z). In respect of periodic DFT calculations, we are grateful to the UK Materials and Molecular Modelling Hub for computational resources, which is partially funded by EPSRC (EP/T022213/1, EP/W032260/1 and EP/P020194/1). We also thank the EPSRC UK National Crystallography Service at the University of Southampton, and the University of Reading's Chemical Analysis Facility, for the collection of the crystallographic data. Hao Lan would like to thank the Bristol Chemical Synthesis CDT, funded by EPSRC (EP/L015366/1), for a PhD studentship. Finally, we thank Prof. Christina Redfield, the University of Oxford, for the help with using 950 MHz ultra‐high resolution NMR spectrometer. Funding Information: We thank The Leverhulme Trust for funding from a Research Project Grant (RPG-2019-283), in addition to King's College London and the China Scholarship Council (Studentship to QL) as well as the Wellcome Trust and the Royal Society (Sir Henry Dale Fellowship to MM, 202250/Z/16/Z). In respect of periodic DFT calculations, we are grateful to the UK Materials and Molecular Modelling Hub for computational resources, which is partially funded by EPSRC (EP/T022213/1, EP/W032260/1 and EP/P020194/1). We also thank the EPSRC UK National Crystallography Service at the University of Southampton, and the University of Reading's Chemical Analysis Facility, for the collection of the crystallographic data. Hao Lan would like to thank the Bristol Chemical Synthesis CDT, funded by EPSRC (EP/L015366/1), for a PhD studentship. Finally, we thank Prof. Christina Redfield, the University of Oxford, for the help with using 950 MHz ultra-high resolution NMR spectrometer. Publisher Copyright: {\textcopyright} 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",
year = "2023",
month = sep,
day = "4",
doi = "10.1002/anie.202305326",
language = "English",
volume = "62",
journal = "ANGEWANDTE CHEMIE-INTERNATIONAL EDITION",
issn = "1433-7851",
publisher = "WILEY-BLACKWELL",
number = "36",
}