Virtual screening and experimental validation reveal novel small-molecule inhibitors of 14-3-3 protein-protein
Philipp Thiel1, Lars Röglin, Nicole Meissner
1Chemical Genomics Centre of the Max Planck Society, Otto-Hahn-Straße 15, D-44227 Dortmund, Germany.
Abstract:
We report first non-covalent and exclusively extracellular inhibitors of 14-3-3 protein-protein interactions identified by virtual screening. Optimization by crystal structure analysis and in vitro binding assays yielded compounds capable of disrupting the interaction of 14-3-3σ with aminopeptidase N in a cellular assay.


