Redox manipulation of enzyme activity through physiologically active molecule

Dao Lin; Yuhe Kan; Liang Yan; Yongqi Ke; Yang Zhang; Hang Luo; Xinjing Tang; Xiangjun Li; Yujian He; Li Wu

doi:10.1016/j.isci.2021.102977

Redox manipulation of enzyme activity through physiologically active molecule

iScience. 2021 Aug 14;24(9):102977. doi: 10.1016/j.isci.2021.102977. eCollection 2021 Sep 24.

Authors

Dao Lin¹, Yuhe Kan¹, Liang Yan¹, Yongqi Ke¹, Yang Zhang¹, Hang Luo¹, Xinjing Tang², Xiangjun Li¹, Yujian He¹, Li Wu^{1

2}

Affiliations

¹ School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 101408, China.
² State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

Abstract

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.

Keywords: Biochemical Mechanism; Biochemistry Applications; Cancer; Medical Biochemistry.