Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Lab of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Angew Chem Int Ed Engl. 2021 Jan 25;60(4):2099-2103. doi: 10.1002/anie.202012470. Epub 2020 Nov 23.
It is commonly considered that amyloid-β (Aβ) fibrils are heavily involved in the neurological diseases. Establishing an external model based on the core recognition motif (diphenylalanine, FF) of Aβ would be of significance in understanding the assembly and disassembly of Aβ fibrils in living system. Herein, supramolecular gels with structure transition from amyloid-like β-sheet to different supramolecular helices were obtained through the co-assembly of a N-fluorenylmethoxycarbonyl-protected L-FF (L-FmocFF) with achiral pyridine derivatives. It is found that the different stacking modes (H- or J-aggregates) of additives and the microenvironment of chiral carbon play vital roles for the selectively chiral transfer or amplification of L-FmocFF. The dynamic process of helix formation was also captured. This work provides a convenient co-assembly way to explore the structure basis of Aβ fibrils with a controlled chirality.
普遍认为淀粉样蛋白-β（Aβ）纤维在神经疾病中起重要作用。基于 Aβ的核心识别模体（二苯丙氨酸，FF）建立外部模型对于理解 Aβ纤维在活系统中的组装和拆卸具有重要意义。在此，通过 N-芴甲氧羰基保护的 L-FF（L-FmocFF）与非手性吡啶衍生物的共组装，获得了具有结构从淀粉样β-折叠到不同超分子螺旋转变的超分子凝胶。研究发现，添加剂的不同堆积模式（H 或 J 聚集体）和手性碳的微环境对 L-FmocFF 的选择性手性传递或放大起着至关重要的作用。还捕获了螺旋形成的动态过程。这项工作提供了一种方便的共组装方法，用于探索具有控制手性的 Aβ纤维的结构基础。
