Biological Targets B4: Modulation of 14-3-3 protein-protein interactions by supramolecular chemistry

Dr. Christian Ottmann

This project has been finished in 2020.

Project area B4 has mechanistically and structurally characterized the effect of molecular tweezers and combinatorial ligands on various 14-3-3 proteins with a particular focus on prominent 14-3-3 targets such as Raf kinases, p53 and aminopeptidase N (CD13). Protein crystallography in tandem with biophysical methods like SPR, thermophoresis and ITC have been employed to draw a picture of the mechanistic basis of these modulations, which have been further refined by MD simulations and QM/MM calculations. The most potent binders have been used to modulate the extracellular 14-3-3 protein-protein interactions with aminopeptidase N (CD13).