Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands
The modulation of Protein-Protein Interactions (PPIs) is one of the most promising and active fields in modern drug discovery. Whereas the inhibition of PPIs is a well-recognized field, targeted stabilization of PPIs is under-represented. In this talk, a case is made for stabilization of interactions of the hub protein 14-3-3 with its partner proteins. This stabilization has the potential to result in therapeutic benefits in disease areas as diverse as in cancer, cystic fibrosis, inflammation, metabolic diseases, and neurodegeneration. The chemistry to target 14-3-3 PPIs range from fragments, over macrocycles and natural products to supramolecular ligands. To make the 14-3-3 protein class accessible for drug discovery combined with the strategy of PPI stabilization may hold considerable potential for future drug discovery.
Keywords: Fragment-based ligand discovery, macrocycles, Natural Products, Protein-Protein Interactions, supramolecular ligands.