Lin Qi, Lan Hao, Ma Chunmiao, Stendall Ryan T, Shankland Kenneth, Musgrave Rebecca A, Horton Peter N, Baldauf Carsten, Hofmann Hans-Jörg, Butts Craig P, Müller Manuel M, Cobb Alexander J A
Department of Chemistry King's College London 7 Trinity Street London SE1 1DB UK.
School of Chemistry University of Bristol Cantocks Close Bristol BS8 1TS UK.
Angew Chem Weinheim Bergstr Ger. 2023 Sep 4;135(36):e202305326. doi: 10.1002/ange.202305326. Epub 2023 Jun 14.
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.
我们报道了由α-氨基酸和δ-氨基酸的1:1异源序列形成的不寻常的13/11螺旋（交替的i，i + 1 {NH - O = C}和i，i + 3 {C = O - H - N}氢键）的首个核磁共振（NMR）和X射线衍射（XRD）结构，并展示了该框架在催化方面的应用。虽然分子内氢键（IMHBs）是该体系中螺旋形成的明确驱动力，但我们还观察到一个δ-氨基酸的乙基残基与序列中下一个δ-残基的环己基之间存在非极性相互作用，这种相互作用似乎使一种螺旋比另一种更稳定。据我们所知，以前尚未观察到这种导致特定螺旋偏好的额外稳定作用类型。至关重要的是，所形成的螺旋类型将α-残基官能团置于足够近的位置，以便参与双功能催化，这在我们将该体系用作简约型醛缩酶模拟物的应用中得到了证明。
