Stabilization of protein-protein interactions by small molecules

Area of Science:

• Biochemistry
• Drug Discovery
• Molecular Biology

Background:

• Protein-protein interactions (PPIs) are crucial in disease pathogenesis.
• Inhibiting PPIs is a validated therapeutic approach, but stabilizing PPIs remains underexplored.
• Natural products like FK506 demonstrate the physiological relevance of PPI stabilization.

Purpose of the Study:

• To highlight the therapeutic potential of stabilizing protein-protein interactions (PPIs) with small molecules.
• To underscore the underrepresentation of PPI stabilization strategies in scientific literature.
• To showcase recent advancements in synthetic molecules that stabilize PPIs.

Main Methods:

• Literature review of existing research on PPI modulation.
• Analysis of natural products known to stabilize PPIs.
• Examination of recent drug discovery projects reporting PPI-stabilizing synthetic molecules.

Main Results:

• PPI stabilization is a viable strategy with significant therapeutic potential.
• Few synthetic molecules have been reported for targeted PPI stabilization.
• Emerging synthetic compounds effectively stabilize homo- and hetero-oligomeric protein complexes.

Conclusions:

• Targeted PPI stabilization represents a largely untapped area in drug discovery.
• Developing small molecules that stabilize PPIs can significantly expand the druggable genome.
• Further research into PPI stabilization is warranted to develop novel therapeutics.