Supramolecular Chemical Biology – Where weak interactions become strong
Protein-Protein Interactions (PPIs) lie at the heart of cellular signalling, but are virtually unexplored from a drug discovery perspective. Especially small molecule stabilization of PPIs (molecular glues) offers enormous opportunities for providing insight in the molecular regulation mechanisms of PPIs and for drug development. Our group uses supramolecular chemical biology to unravel the underlying, complex, molecular interaction mechanisms of PPIs, with the overall aim to enable innovative medicinal chemistry to stabilize PPIs. Especially fundamental supramolecular concepts such as cooperativity and multivalency drive our chemical biology to develop selective small molecules as probes and drug starting points. Using nuclear receptors and 14-3-3 proteins as examples this presentation aims to provide insights into questions such as 1) How can supramolecular chemical biology steer medicinal chemistry? 2) What are the key biophysical characteristics of molecules that stabilize PPIs? and 3) How can we find chemical starting point for PPI stabilization?
Luc Brunsveld, performed his Ph.D. research at TU/e and the University of Illinois at Urbana-Champaign (USA) in the field of supramolecular chemistry, under supervision of Prof. E.W. (Bert) Meijer (2001). He was a postdoctoral fellow with Prof. Herbert Waldmann at the Max-Planck Institute of Molecular Physiology (Dortmund, Germany) working on protein semi-synthesis (2001-2002), followed by two years as a group leader in medicinal chemistry at Organon. In 2005, he started a research group at MPI in Dortmund working on supramolecular chemical biology. In 2008, he moved to TU/e where he was appointed Full Professor of Chemical Biology. Luc’s awards include the NVBMB Award of the Dutch Society for Biochemistry and Molecular Biology, the Gold Medal of the Royal Netherlands Chemical Society KNCV, and an NWO Vici grant. Luc Brunsveld is scientific co-founder of Ambagon Therapeutics (2020).