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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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Science China Chemistry 2023年第7期66卷 2053-2061页

作者： Haixiao Fang Panpan Li Congzhen Shen Fang Tang Aixiang Ding Hua Bai Bo Peng Xuekang Yang Zhengqiu Li Kai Huang Sijun Pan Lin Li Wei Huang The Institute of Flexible Electronics(IFE Future Technologies)Xiamen UniversityXiamen 361005China Future Display Institute in Xiamen Xiamen 361005China Frontiers Science Center for Flexible Electronics Xi’an Institute of Flexible Electronics(IFE)and Xi’an Institute of Biomedical Materials&EngineeringNorthwestern Polytechnical UniversityXi’an 710072China School of Pharmacy Jinan UniversityGuangzhou 510632China Xijing Hospital The Fourth Military Medical UniversityXi’an 710032China

Monoamine oxidase A(MAO-A)plays a critical role in the development of glioma and other neurological *** 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 ***-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 ***,we report HD1 as the first fluorogenic-inhibitor-based probe that can selectively label endogenous MAO-A from various mammalian cells and clinical *** 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 *** the excellent binding affinity(in vitro K_(i)=285 n M)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.

关键词： monoamine oxidase A fluorogenic-inhibitor-based probe super-resolution imaging activity-based protein profiling glioma

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