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Molecular glues to stabilise protein-protein interactions
Lorenzo Soini1, Seppe Leysen2, Jeremy Davis3
1Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands; Department of Structural Biology and Biophysics, UCB Biopharma UK, Slough, UK.
Current Opinion in Chemical Biology
|June 24, 2022
Summary
Targeting protein-protein interactions (PPIs) offers therapeutic potential for diseases. Stabilizing PPIs, particularly with 14-3-3 proteins, is a promising new drug discovery strategy.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Protein-protein interactions (PPIs) are crucial in cellular signaling pathways.
- Dysregulated PPIs are implicated in the pathology of various diseases.
- Modulating PPIs presents significant therapeutic opportunities.
Purpose of the Study:
- To explore the therapeutic potential of modulating protein-protein interactions (PPIs).
- To highlight the emerging strategy of stabilizing PPIs for drug discovery.
- To introduce 14-3-3 proteins as potential targets for PPI stabilization therapies.
Main Methods:
- Review of existing literature on PPI modulation strategies.
- Analysis of the role of PPI stabilization in targeted protein degradation (TPD).
- Examination of 14-3-3 proteins as a class of interaction partners.
Main Results:
- Inhibition of PPIs was an initial therapeutic approach.
- Stabilization of PPIs is now recognized as a viable therapeutic strategy.
- Targeted protein degradation (TPD) utilizes PPI stabilization for therapeutic effect.
- 14-3-3 proteins represent a novel target class for PPI stabilization-based drug discovery.
Conclusions:
- Modulating protein-protein interactions (PPIs) is a key strategy in disease treatment.
- Stabilizing PPIs, including those involving 14-3-3 proteins, offers new therapeutic avenues.
- Targeted protein degradation (TPD) and 14-3-3 protein interactions are promising areas for future drug development.
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