Biomimetic single Al-OH site with high acetylcholinesterase-like activity and self-defense ability for neuroprotection

Nature Communications

Article

Lirong Zheng¹  Xiaowen Cui¹  Xiaoli Cai²  Yuteng Huang²  Qihui Zheng²  Chengzhou Zhu³  Weiqing Xu³  Yating Wen³  Yu Zhang³  Wenling Gu³  Rina Su³  Yu Wu³  Shipeng Zhang⁴  Shaojun Guo⁴  Liuyong Hu⁵  Weiyu Song⁶ 

[1] Beijing Synchrotron Radiation Facility, Institute of High Energy Physics Department, Chinese Academy of Sciences Institution, 100049, Beijing, P.R. China;Department of Nutrition, Hygiene and Toxicology, School of Public Health, Medical College, Wuhan University of Science and Technology, 430065, Wuhan, P.R. China;National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, 430079, Wuhan, P.R. China;School of Materials Science and Engineering, Peking University, 100871, Beijing, P.R. China;School of Materials Science and Engineering, Wuhan Institute of Technology, 430205, Wuhan, P.R. China;State Key Laboratory of Heavy Oil Processing, College of New Energy and Materials, China University of Petroleum, 102249, Beijing, P.R. China;

关键词: ;   

DOI  :  10.1038/s41467-023-41765-x

 received in 2023-04-14, accepted in 2023-09-19,  发布年份 2023

来源: Springer

【 摘 要 】

Neurotoxicity of organophosphate compounds (OPs) can catastrophically cause nervous system injury by inhibiting acetylcholinesterase (AChE) expression. Although artificial systems have been developed for indirect neuroprotection, they are limited to dissociating P-O bonds for eliminating OPs. However, these systems have failed to overcome the deactivation of AChE. Herein, we report our finding that Al3+ is engineered onto the nodes of metal–organic framework to synthesize MOF-808-Al with enhanced Lewis acidity. The resultant MOF-808-Al efficiently mimics the catalytic behavior of AChE and has a self-defense ability to break the activity inhibition by OPs. Mechanism investigations elucidate that Al3+ Lewis acid sites with a strong polarization effect unite the highly electronegative –OH groups to form the enzyme-like catalytic center, resulting in superior substrate activation and nucleophilic attack ability with a 2.7-fold activity improvement. The multifunctional MOF-808-Al, which has satisfactory biosafety, is efficient in reducing neurotoxic effects and preventing neuronal tissue damage.

【 授权许可】

CC BY   
© Springer Nature Limited 2023

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