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Updated: Jun 24, 2026
Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
Published on: October 10, 2020
A novel method for screening the glutathione transferase inhibitors
Zhijun Wang1, Li Jin, Grzegorz Wegrzyn
1CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031, Shanghai, PR China. zjwang@shmu.edu.cn
Background:
Glutathione transferases (GSTs) belong to the family of Phase II detoxification enzymes. GSTs catalyze the conjugation of glutathione to different endogenous and exogenous electrophilic compounds. Over-expression of GSTs was demonstrated in a number of different human cancer cells. It has been found that the resistance to many anticancer chemotherapeutics is directly correlated with the over-expression of GSTs. Therefore, it appears to be important to find new GST inhibitors to prevent the resistance of cells to anticancer drugs. In order to search for glutathione transferase (GST) inhibitors, a novel method was designed.
Results:
Our results showed that two fragments of GST, named F1 peptide (GYWKIKGLV) and F2 peptide (KWRNKKFELGLEFPNL), can significantly inhibit the GST activity. When these two fragments were compared with several known potent GST inhibitors, the order of inhibition efficiency (measured in reactions with 2,4-dinitrochlorobenzene (CDNB) and glutathione as substrates) was determined as follows: tannic acid > cibacron blue > F2 peptide > hematin > F1 peptide > ethacrynic acid. Moreover, the F1 peptide appeared to be a noncompetitive inhibitor of the GST-catalyzed reaction, while the F2 peptide was determined as a competitive inhibitor of this reaction.
Conclusion:
It appears that the F2 peptide can be used as a new potent specific GST inhibitor. It is proposed that the novel method, described in this report, might be useful for screening the inhibitors of not only GST but also other enzymes.
Insights
Two novel peptides, F1 and F2, were identified as potent inhibitors of glutathione transferases (GSTs). The F2 peptide, a competitive inhibitor, shows promise for overcoming anticancer drug resistance by targeting GST activity.
Area of Science:
- Biochemistry
- Enzymology
- Pharmacology
Background:
- Glutathione transferases (GSTs) are Phase II detoxification enzymes crucial in metabolizing endogenous and exogenous compounds.
- Over-expression of GSTs in cancer cells correlates with resistance to chemotherapeutic agents.
- Targeting GSTs is a key strategy to enhance the efficacy of anticancer drugs.
Purpose of the Study:
- To design and implement a novel method for identifying glutathione transferase (GST) inhibitors.
- To evaluate the inhibitory potential of newly discovered GST fragments against GST activity.
Main Methods:
- Development of a novel screening method for GST inhibitors.
- Comparative analysis of F1 and F2 peptide inhibition efficiency against known GST inhibitors.
- Determination of inhibition kinetics (competitive vs. noncompetitive) for F1 and F2 peptides.
Main Results:
- Two GST fragments, F1 peptide (GYWKIKGLV) and F2 peptide (KWRNKKFELGLEFPNL), demonstrated significant inhibition of GST activity.
- Inhibition efficiency order: tannic acid > cibacron blue > F2 peptide > hematin > F1 peptide > ethacrynic acid.
- F1 peptide acted as a noncompetitive inhibitor, while F2 peptide exhibited competitive inhibition.
Conclusions:
- The F2 peptide is identified as a potent and specific inhibitor of glutathione transferase.
- The developed novel method shows potential for screening inhibitors of GST and other enzymes.
