Redox manipulation of enzyme activity through physiologically active molecule

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.