硝基还原酶
取代基
荧光
硝基
化学
缺氧(环境)
选择性
菁
生物物理学
立体化学
生物化学
生物
氧气
酶
催化作用
有机化学
物理
烷基
量子力学
作者
Xianghan Zhang,Zhiqing Gao,Yuqiong Xia,Qunyan Dong,Yutian Cao,Qian Jia,Fang Sun,Lingling Zheng,Chu Tang,Jie Yu
标识
DOI:10.1016/j.saa.2022.121031
摘要
Nitroreductase (NTR) detection in tumor is critical because NTR level is correlated with hypoxia degree and cancer prognosis. With the feature of high sensitivity and selectivity, fluorescence organic probes for NTR detection exhibited a promising future for tumor hypoxia detection. However, the discovery and design of such probes have been impeded due to the lack of the understanding of spatial match and mismatch of these probes with NTR. Here, we have developed two new nitrophenyl-functionalized trimethincyanine (Cy3) probes with para- or meta- positions of nitro-group in phenyl ring. Para-nitrophenyl substituted Cy3 (pNP-Cy3) exhibited a remarkable response to NTR (20-fold fluorescence enhancement) with good selectivity and sensitivity. Experimental and theoretical analysis verified that the substituent position of nitro group on phenyl ring of dyes altered the spatial arrangement of nitro-substituent group, thereby modulated the spatial match and mismatch between Cy3 dyes and binding domain of NTR, and consequently led to a different fluorescent turn-on response. In tumor-bearing mice model, hypoxia status of A549 xenografted tumor of mice was successfully delineated by using pNP-Cy3. These results may provide a clue for designing new cyanine-derived NTR probe to monitor NTR-overexpressed hypoxia cancer cells.
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