Abstract

Our group combines organic synthesis, protein chemistry, structural biology, and supramolecular chemistry to perform chemical biology studies on protein-protein interactions (PPIs) with the aim to enable innovative medicinal chemistry for ‘molecular glues’ for PPIs. In this presentation I aim to show that a “supramolecular” point of view to protein-protein interactions (PPIs) helps to unravel the underlying, more complex, interaction mechanisms. This conceptual approach to PPIs allows to recognize and apply concepts such as multivalency and cooperativity within the context of drug discovery. Using nuclear receptors and 14-3-3 proteins as examples this presentation aims to provide insights into questions such as 1) How can chemical biology studies steer medicinal chemistry for PPIs? 2) What are the key biophysical characteristics of molecules that stabilize PPIs? 3) How can we find chemical starting point for PPI stabilization?