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Affinity-based small fluorescent probe for NAD(P)H:quinone oxidoreductase 1 (NQO1). Design, synthesis and
Jinlei Bian1, Xiang Li1, Lili Xu1
1State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China.
Abstract:
NQO1 is a dimeric flavoprotein which intimately associated with cancer and overexpressed in the cytosol of numerous human tumor cells. Given that the cellular environment is quite dynamic and versatile, further investigation of the function of NQO1 depends on tools for specific detection of it. Currently, several activity-based assays have been developed to detect NQO1-expressing cancerous tissues. Herein, we report the development of a functional affinity-based small-molecule probe which is composed of a potent small-molecule NQO1 inhibitor 3d as the recognition group, a linker and the fluorophores group FITC. The probe exhibits good inhibitory activity of NQO1 and has been successfully used to label the protein in A549 cells at the micromolar level. These features make the probe favorable for mechanistic studies and cancer diagnostic biomarker. Based on these preliminary results, our laboratory will focus on the further development of fluorescent probe for NQO1, which could be anticipated to be applied in physiological and pathological studies of NQO1.
