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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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Specific tracking of monoamine oxidase a in heart failure models by a far-red fluorescent probe with an ultra large Stokes shift

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Chinese Chemical Letters 2022年第3期33卷 1572-1576页

作者： Xinming Li Donglei Shi Yihe Song Yixiang Xu Ying Gao Wenjing Qiu Xin Chen Xiaokang Li Yunyuan Huang Yanjun Feng Baoli Li Yuan Guo Jian Li State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug DesignSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education College of Chemistry and Materials ScienceNorthwest UniversityXi'an 710127China Frontiers Science Center for Materiobiology and Dynamic Chemistry East China University of Science and TechnologyShanghai 200237China College of Pharmacy and Chemistry Dali UniversityDali 671000China Clinical Medicine Scientific and Technical Innovation Center Shanghai Tenth People's HospitalTongji University School of MedicineShanghai 200092China

monoamine oxidase a(MAO-A) is a prominent myocardial source of reactive oxygen species(ROS), and its expression and activity are strongly increased in failing hearts. Therefore, accurate evaluation of MAOA activity in cardiomyocytes is of great importance for understanding its biological functions and early diagnosing the progression of heart failure. However, so far, there is no report on the fluorescent diagnosis of heart failure by a specific probe for MAO-A. In this work, two far-red emissive fluorescent turn-on probes(KXS-M1 and KXS-M2) for the highly selective and sensitive detection of MAO-A were *** probes exhibit good response to MAO-A, one of which, KXS-M2, performs better than the other one in terms of a fluorescence increment and sensitivity. Using the pioneering probe KXS-M2, specific fluorescence imaging of MAO-A in glucose-deprived H9c2 cardiac cells, zebrafish and isoprenaline-induced failing heart tissues was achieved, proving that KXS-M2 can serve as a powerful tool for the diagnosis and treatment of heart failure.

关键词： Heart failure monoamine oxidase a Oxidative stress Fluorescent probe Far-red emission Diagnosis

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Rational Design of Two-photon Fluorogenic Probe for Visualizing monoamine oxidase a Activity in Live Cells and Tissues

Rational Design of Two-photon Fluorogenic Probe for Visualiz...

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第十一届全国化学生物学学术会议

作者： Haixiao Fang Hang Zhang Lin Li Chengwu Zhang Qiong Wu Shao Q.Yao Wei Huang Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM) Nanjing Tech University (NanjingTech)

monoamine oxidases(MAOs) are important mammalian enzymes that catalyze the transformation of various neurotransmitters including serotonin,dopamine,phenethylamine,and others. They are normally expressed on the outer membrane of mitochondria in *** human,MAOs have been found to play key roles in maintaining the homeostasis of *** present,there are two known human MAOs(***-A and MAO-B),which,despite high sequence homology(～70%),differ significantly in their biological roles,cell distributions and substrate specificity. The ability to differentiate them by using fluorescence etection/imaging technology is of significant biological relevance,but highly challenging with available chemical ***,we report the first MAO-A specific two-photon fluorogenic probe(F1),capable of selective imaging of endogenous MAO-A enzymatic activities from a variety of different biological samples,including MAO-A expressing neuronal SY-SY5Y cells and the brain of tumor-bearing mice,by using two-photon fluorescence microscopy(TPFM) without toxicity at working concentrations.

关键词： monoamine oxidase a MPTP two photon fluorogenic probes molecular docking

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