Lin Dao, Kan Yuhe, Yan Liang, Ke Yongqi, Zhang Yang, Luo Hang, Tang Xinjing, Li Xiangjun, He Yujian, Wu Li
School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 101408, China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
iScience. 2021 Aug 14;24(9):102977. doi: 10.1016/j.isci.2021.102977. eCollection 2021 Sep 24.
The effective utility of physiologically active molecules is crucial in numerous biological processes. However, the regulation of enzyme functions through active substances remains challenging at present. Here, glutathione (GSH), produced in cells, was used to modulate the catalytic activity of thrombin without external stimulus. It was found that high concentrations of GSH was more conducive to initiate the cleavage of compound AzoDiTAB in the range of concentration used to mimic the difference between cancer and normal cells, which has practical implications for targeting cancel cells since GSH is overexpressed in cancer cells. Importantly, GSH treatment caused the deformation of G4 structure by cleaving AzoDiTAB and thus triggered the transition of thrombin from being free to be inhibited in complex biological systems. This work would open up a new route for the specific manipulation of enzyme-catalyzed systems in cancer cells.
生理活性分子的有效效用在众多生物过程中至关重要。然而，目前通过活性物质调节酶功能仍然具有挑战性。在这里，细胞内产生的谷胱甘肽（GSH）被用于在无外部刺激的情况下调节凝血酶的催化活性。发现在用于模拟癌细胞与正常细胞差异的浓度范围内，高浓度的GSH更有利于引发化合物AzoDiTAB的裂解，由于GSH在癌细胞中过表达，这对于靶向癌细胞具有实际意义。重要的是，GSH处理通过裂解AzoDiTAB导致G4结构变形，从而在复杂生物系统中触发凝血酶从游离状态转变为被抑制状态。这项工作将为癌细胞中酶催化系统的特异性操纵开辟一条新途径。
