Fluorogenic and Mitochondria-Localizable Probe Enables Selective Labeling and Imaging of Nitroreductase

Nitroreductase (NTR), one of the flavin-dependent enzymes and an upregulated enzyme under tumor hypoxia, has been studied for decades. Many fluorescent probes were developed to detect NTR activity; however, these probes tend to diffuse away from their reaction site (NTR) inevitably, leading to inapp...

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Published in:Analytical chemistry (Washington) 2022-05, Vol.94 (20), p.7272-7277
Main Authors: Wang, Shuyi, Tan, Wei, Lang, Wenjie, Qian, Huijuan, Guo, Shuhong, Zhu, Liquan, Ge, Jingyan
Format: Article
Language:English
Subjects:
Chemistry
Fixation
Flavin
Fluorescence
Fluorescent indicators
Hypoxia
Labeling
Localization
Mitochondria
Nitroreductase
Probes
Quinones
Signal to noise ratio
Spatial discrimination
Spatial resolution
Tumors
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Summary:Nitroreductase (NTR), one of the flavin-dependent enzymes and an upregulated enzyme under tumor hypoxia, has been studied for decades. Many fluorescent probes were developed to detect NTR activity; however, these probes tend to diffuse away from their reaction site (NTR) inevitably, leading to inappropriate sample fixation, lower accuracy of NTR localization, and weaker signal-to-noise ratio. Herein, we present the design, synthesis, in vitro evaluation, and biological applications of an NTR-activatable fluorogenic and labeling probe FY. By integrating with quinone methide (QM) proximity-based protein labeling, the additional fluoromethyl group on FY serves as a potential origin of QM. Compared with conventional fluorescent probes, this new NTR probe not only offers mitochondrial localizable and fluorogenic response but also achieves permanent retention on the site of activation with an enhanced spatial resolution to improve the detection sensitivity even after cell fixation. We believe our work could offer an expandable synthetic approach to develop these permanent labeling and imaging fluorescence probes for deciphering complex biological events.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.2c00512