Brunsveld Lab

Eindhoven University of Technology

Zuid-Nederland (NL4) · Netherlands

ERC-funded
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ERC Advanced Grant · 2022

Stabilization of Protein Protein Interactions; transforming molecular glue discovery from art into science

Intrinsically Disordered Proteins (IDPs) represent one of drug discovery’s major challenges. Due to their high degree of conformational freedom, IDPs have no defined pockets for binding small molecules. Molecular glues that can strengthen protein-protein interactions (PPIs) are a revolutionary technology for drug discovery. The hub protein 14-3-3 regulates many IDPs via phosphorylation-dependent PPIs. Stabilization of 14-3-3 PPIs with small molecular glues provides a unique entry point to render IDPs druggable and mitigate the aberrant behaviour of malfunctioning IDPs, for example in neurodegenerative diseases. While inhibition of PPIs by small molecules has expanded the proteome suitable…

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