UCSF and Technical University of Eindhoven investigators have identified molecular fragments that stabilize 14-3-3/phospho-peptide and 14-3-3/phospho-protein interactions. Further structure-guided and empirical medicinal chemistry will lead to a drug lead for the most advanced target (estrogen receptor).
Systematic approaches to stabilizing protein-protein interactions are nonexistent in the literature; this particular focus on 14-3-3/client complexes allows researchers to address many high-value targets in oncology, neurodegeneration, inflammation, and metabolism.
To date, the demonstration of the discovery/linking method is unique for this target and for stabilizing protein-protein interactions in general. By identifying the underlying rules for molecular recognition of 14-3-3/clients by small molecules, these hit compounds may also be starting points to discover stabilizers for new 14-3-3/client complexes.
To develop & commercialize the technology for drug development.
Proof of Concept