Biomimetic Phosphohydrolase Nanozyme Based on Defect-Engineered Metal-Organic Framework  

作　　者：Xiaoxue Kou Yuhong Lin Yong Shen Linjing Tong Rui Gao Suya Liu Siming Huang Fang Zhu Guosheng Chen Gangfeng Ouyang 

机构地区：[1]MOE Key Laboratory of Bioinorganic and Synthetic Chemistry,School of Chemistry,Sun Yat-sen University,Guangzhou 510006 [2]Shanghai NanoPort,Thermo Fisher Scientific,Pudong District,Shanghai 200120 [3]Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology,The NMPA and State Key Laboratory of Respiratory Disease,School of Pharmaceutical Sciences and The Fifth Affiliated Hospital,Guangzhou Medical University,Guangzhou 511436

出　　处：《CCS Chemistry》2024年第7期1821-1835,共15页中国化学会会刊（英文）

基　　金：financially supported by the projects of the National Natural Science Foundation of China (grant nos.22174164,G.C.,22104159,S.H.);the Natural Science Foundation of Guangzhou City (grant no.202201011408,G.C.);the Fundamental Research Funds for the Central Universities,and Sun Yat-sen University (grant no.23lgbj005,G.C.).

摘　　要：Phosphodiester bonds are the backbone linkages of all the nucleic acids which store and transfer biological information.The hydrolysis of phosphodiester bonds is of great importance to the replication,recombination,and damage repair of DNA as well as the maturation and processing of RNA.However,the spontaneous scission of individual phosphodiester linkages is kinetically challenging under physiological conditions,with an estimated half-life of 30 million years.Here,we discover a defect-engineered Zr-metal-organic framework(Zr-MOF)nanozyme containing cluster-missing reo defects,named UiO-66 REO,that possesses intrinsic phosphodiesterase-like activity that allows for the cleavage of the phosphodiester bond in physiological condition(pH=7.4 and 37℃),outperforming the activityrecording Zr-MOFs.The atomic-level structure of the UiO-66 REO nanozyme has been directly identified by the synchrotron radiation absorption spectrum and integrated differential phase contrast-scanning transmission electron microscopy.We find that both the defective boundary regions and unusual Zr6-clusters formed in the reo phase of the UiO-66 REO nanozyme contribute to the improvement in efficiency of phosphodiesterase-like hydrolysis,which realizes the cleavage of DNA in mild conditions.This work offers a new insight into biomimetic enzymology using crystal and defect engineering and opens up new possibilities for the development of low-cost,structurally stable and sustainable phosphodiesterase nanozymes for different biological applications.

关 键 词：nanozyme metal-organic framework biomimetic catalysis hydrolase-like activity defective engineering 

分 类 号：O62[理学—有机化学]