手性多酸簇界面的构筑及其对淀粉样多肽的识别与电化学调控

The inhibition of amyloid β-peptide (Aβ) fibrosis is a research hotspot in the treatment of Alzheimer's disease, interfacial chirality and electrostatic interaction are already proved to have the capability to affect its aggregation behavior. However, the electrochemical regulation of Aβ on the chiral interface has not yet been achieved. In this project, magnetron sputtering method is adopted to prepare gold film with nanoscale thickness on the indium tin oxide conductive glass, then chiral polyoxometalate clusters possessing excellent electrochemical properties are assembled onto the gold-modified conductive substrate through a supramolecular interfacial assembly process. The obtained two dimensional chiral interface exhibits different chiral features and in-situ electrochemical responsiveness. Through the investigation of the adsorption and assembly change under the electrochemical control on the chiral interface, the influence of interfacial chirality and electrochemical property on the Aβ assembly behaviors can be explored, and it is expected to find an approach to efficiently inhibit the Aβ fibrosis. Finally, in combination with the characterization and theoretical simulation of interfacial properties, the synergistic effect of interfacial chirality and electrochemical properties on the adsorption and assembly behavior of Aβ could be elucidated. We hope that this project can enrich the construction method of chiral interface, promote the bio-application of chiral polyoxometalate and provide new strategy for understanding the phenomena related to chirality and electrochemical property in biological systems.

β淀粉样多肽（Aβ）的纤维化聚集抑制是阿尔兹海默病治疗的研究热点，界面手性和静电作用已被证明能影响其聚集行为，然而手性界面上Aβ多肽的电化学调控至今还未实现。本项目采用磁控溅射的方法，首先在氧化铟锡导电玻璃上制备纳米厚度的金膜，然后基于超分子界面组装过程，将具有优异电化学性质的手性多酸簇组装到金修饰的导电基底上，进而制备得到具有不同手性的、可原位电化学调控的二维手性界面。利用手性界面考察Aβ的吸附差异和电化学调控状态下组装结构的变化，分析不同界面手性和电化学性质对于Aβ多肽组装行为的影响规律，并实现Aβ纤维化聚集的高效抑制。最后，结合手性界面性质的表征和理论模拟，阐明界面手性和电化学性质对于Aβ吸附和组装行为的协同影响机理。我们希望本项目能够拓展手性界面的构筑方法、促进手性多酸簇的生物应用研究、为理解生物体系中手性和电化学现象提供新的研究思路。

近年来，手性界面上精准调控多肽组装和细胞粘附等行为吸引了越来越多的关注。然而，结构有序的单层手性界面构筑仍然存在巨大挑战。多金属氧簇是一种无机簇合物，具有纳米尺度的精确结构，其与金基底可形成强配位作用和有序堆积结构。因此，本项目于磁控溅射的方法制备得到了平整的镀金薄膜，并遴选结构稳定的手性多金属氧簇作为组装材料，通过界面超分子组装实现了手性界面构筑。研究了不同手性界面上淀粉样多肽聚集和大肠杆菌、金黄色葡萄球菌等细胞的粘附行为，基于此探索了界面性质对多肽、细胞行为调控等影响机制。项目基本完成了预定研究目标，主要取得了以下研究成果：1. 设计构建了单层手性分子有序堆积的手性界面；2. 实现了手性界面上淀粉样多肽的聚集抑制和细胞粘附调控；3. 阐明了手性因素在界面多肽和细胞调控中的作用。在该项目的支持下，发表相关研究论文4篇，申请国家发明专利2项，培养硕士生2名。