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A fluorogenic-inhibitor-based probe for profiling and imaging of monoamine oxidase A in live human glioma cells and clinical tissues

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Abstract

Monoamine oxidase A (MAO-A) plays a critical role in the development of glioma and other neurological disorders. Specific analysis of MAO-A activities and its drug interactions in intact tissue is important for biological and pharmacological research, but highly challenging with current chemical tools. Fluorogenic-inhibitor-based probes offer improved selectivity, sensitivity, and effectiveness to image and profile endogenous targets in an activity-based manner from mammalian cells, which are however rare. Herein, we report HD1 as the first fluorogenic-inhibitor-based probe that can selectively label endogenous MAO-A from various mammalian cells and clinical tissues. The probe was delicately designed based on N-propargyl tetrahydropyridine, a small MAO-A-specific fluorogenic and inhibitory war-head, so that the probe becomes fluorescent upon in situ enzymatic oxidation and covalent labeling of MAO-A. With the excellent binding affinity (vin itro Ki = 285 nM) and fluorogenic properties, HD1 offers a promising approach to simultaneously image endogenous MAO-A activities by super-resolution fluorescence microscopy and study its drug interactions by subsequent activity-based protein profiling, in both live cells and human glioma tissues.

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Acknowledgements

This work was supported by the National Key R&D Program of China (2020YFA0709900), the National Natural Science Foundation of China (62288102, 22077101, 22004099), the Joint Research Funds of Department of Science & Technology of Shaanxi Province and Northwestern Polytechnical University (2020GXLH-Z-008, 2020GXLH-Z-021, 2020GXLH-Z-023), the Natural Science Foundation of Shaanxi Province (2022JM-130), the Key Research and Development Program of Shaanxi (2020ZDLGY13-04) and the Fundamental Research Funds for the Central Universities. The cartoons in Figures 1 and 4 were created using Bio-Render.com. We thank Prof. Stephan A. Sieber (Technical University of Munich) for providing probe P3 and Prof. Shao Q. Yao (National University of Singapore) for providing probes M1-M3.

Author information

Authors and Affiliations

  1. The Institute of Flexible Electronics (IFE, Future Technologies), Xiamen University, Xiamen, 361005, China

    Haixiao Fang, Fang Tang, Aixiang Ding, Sijun Pan, Lin Li & Wei Huang

  2. Future Display Institute in Xiamen, Xiamen, 361005, China

    Haixiao Fang, Fang Tang, Kai Huang, Lin Li & Wei Huang

  3. Frontiers Science Center for Flexible Electronics, Xi’an Institute of Flexible Electronics (IFE) and Xi’an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, Xi’an, 710072, China

    Panpan Li, Hua Bai, Bo Peng, Lin Li & Wei Huang

  4. School of Pharmacy, Jinan University, Guangzhou, 510632, China

    Congzhen Shen & Zhengqiu Li

  5. Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, China

    Xuekang Yang

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  1. Haixiao Fang
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  2. Panpan Li
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  11. Sijun Pan
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Corresponding authors

Correspondence to Sijun Pan, Lin Li or Wei Huang.

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The authors declare no conflict of interest.

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The supporting information is available online at https://chem.scichina.com and https://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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11426_2023_1602_MOESM1_ESM.docx

A Fluorogenic-Inhibitor-Based Probe for Profiling and Imaging of Monoamine Oxidase A in Live Human Glioma Cells and Clinical Tissues

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Fang, H., Li, P., Shen, C. et al. A fluorogenic-inhibitor-based probe for profiling and imaging of monoamine oxidase A in live human glioma cells and clinical tissues. Sci. China Chem. 66, 2053–2061 (2023). https://doi.org/10.1007/s11426-023-1602-7

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  • DOI: https://doi.org/10.1007/s11426-023-1602-7

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