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

Weiqing Xu, Xiaoli Cai, Yu Wu, Yating Wen, Rina Su, Yu Zhang, Yuteng Huang, Qihui Zheng, Liuyong Hu, Xiaowen Cui, Lirong Zheng, Shipeng Zhang, Wenling Gu, Weiyu Song, Shaojun Guo () and Chengzhou Zhu ()
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Weiqing Xu: Central China Normal University
Xiaoli Cai: Medical College, Wuhan University of Science and Technology
Yu Wu: Central China Normal University
Yating Wen: Central China Normal University
Rina Su: Central China Normal University
Yu Zhang: Central China Normal University
Yuteng Huang: Medical College, Wuhan University of Science and Technology
Qihui Zheng: Medical College, Wuhan University of Science and Technology
Liuyong Hu: Wuhan Institute of Technology
Xiaowen Cui: Chinese Academy of Sciences Institution
Lirong Zheng: Chinese Academy of Sciences Institution
Shipeng Zhang: Peking University
Wenling Gu: Central China Normal University
Weiyu Song: China University of Petroleum
Shaojun Guo: Peking University
Chengzhou Zhu: Central China Normal University

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-41765-x

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