A bi-functional fluorescent probe for visualized and rapid natural drug screening via GSTs activity monitoring
A bi-functional fluorescent probe for visualized and rapid natural drug screening via GSTs activity monitoring
复制标题
一种双功能荧光探针，可通过 GST 活性监测进行可视化快速天然药物筛选
DOI：
10.1016/j.snb.2020.129047
复制
发表时间：
2021-02
期刊：
影响因子：
--
通讯作者：
Bin Liu
中科院分区：
文献类型：
--
作者：
Yan Qin;Caiyun Peng;Wei Yang;Jialong Fan;Wen-Bing Sheng;Pan Yi;Yixing Qiu;Huanghe Yu;Sai Jiang;Wei Wang;Bin Liu
谷胱甘肽s -转移酶（GSTs）作为药物筛选的重要靶点，与生理病理过程调控密切相关。因此，对GSTs活性的有效监测有助于GSTs诱导疾病的诊断和治疗药物的发现。间苯二酚型探针具有高灵敏度、高选择性和低细胞毒性，已成为靶标监测的有力工具。本研究设计了一种双功能荧光探针，以间苯二酚为荧光团的间苯二酚型探针（RP）作为GSTs底物和药物筛选工具。GSTs通过催化谷胱甘肽（GSH）与其在RP中的识别位点结合，引发RP的荧光信号显著增强。有意义的是，荧光信号的变化与GSTs活性正相关，可用于监测天然药物对GSTs的调节作用。基于“药物-GSTs活性-荧光信号”的轴向关系，该功能强大的探针通过监测GSTs活性的变化，成功实现了体外GSTs靶向天然化合物的视觉快速筛选。筛选天然化合物1、2和7 （C1、C2和C7）作为GSTs抑制剂，其中C7有助于提高顺铂对癌细胞的敏感性。综上所述，基于双功能荧光探针的天然药物筛选策略在药物快速发现方面具有广阔的应用前景。
Glutathione S-transferase (GSTs), as an important target for drug screening, is closely associated with physiological and pathological process regulation. Hence, effective monitoring of GSTs activity is benificial for GSTs-induced diseases diagnosis and therapeutic drugs discovery. Resorufin-typed probes with high sensitivity, excellent selectivity, and low cytotoxicity have become a powerful tool for target monitoring. In this study, a bi-functional fluorescent probe, resorufin-typed probe (RP) with resorufin as a fluorophore was designed as the GSTs substrate and drug screening tool. GSTs can trigger significant fluorescence signal enhancement of RP by catalyzing the combination of glutathione (GSH) and its recognition site in RP. Meaningfully, the change of fluorescence signal positively correlated with GSTs activity can be used to monitor the regulatory effect of natural drugs on GSTs. Based on the axis relation of “drug-GSTs activity-fluorescence signal”, this powerful probe was successfully employed for visual and rapid screening GSTs-targeted natural compounds in vitro by monitoring the change of GSTs activity. Natural compound 1, 2 and 7 (C1, C2 and C7) were screened as the GSTs inhibitors, and C7 was helpful for enhancing the sensitivity of cisplatin in cancer cells. Overall, the designed natural drug screening strategy based on bi-functional fluorescence probe demonstrated its hopeful application to drug rapid discovery.
登录
查看更多内容
使用半胱胺封端的金纳米粒子作为比色探针目视检测谷胱甘肽 S-转移酶活性和抑制的简单方法
DOI：
10.1007/s13404-015-0171-3
发表时间：
2015-11
期刊：
Gold Bull.
影响因子：
--
作者：
Shan Ren;Fulin Zhou;Chunli Xu;Baoxin Li
通讯作者：
Baoxin Li
影响因子：
3.9
作者：
Deka, Jashmini;Paul, Anumita;Chattopadhyay, Arun
通讯作者：
Chattopadhyay, Arun
影响因子：
15
作者：
Fujikawa, Yuuta;Urano, Yasuteru;Nagano, Tetsuo
通讯作者：
Nagano, Tetsuo
影响因子：
15
作者：
Tsuboi, Katsunori;Bachovchin, Daniel A.;Speers, Anna E.;Spicer, Timothy P.;Fernandez-Vega, Virneliz;Hodder, Peter;Rosen, Hugh;Cravatt, Benjamin F.
通讯作者：
Cravatt, Benjamin F.
影响因子：
4.7
作者：
Gayashani W.M. Sandamalika;Thanthrige Thiunuwan Priyathilaka;D. S. Liyanage;Sukkyoung Lee;H. Lim;Jehee Lee-Jehee
通讯作者：
Gayashani W.M. Sandamalika;Thanthrige Thiunuwan Priyathilaka;D. S. Liyanage;Sukkyoung Lee;H. Lim;Jehee Lee-Jehee