Prof Stefan Knapp studied Chemistry at the University of Marburg (Germany) and at the University of Illinois (USA). He did his PhD in protein crystallography at the Karolinska Institute in Stockholm (Sweden) (1996) and continued his career at the Karolinska Institute as a postdoctoral scientist (1996-1999). In 1999, he joined the Pharmacia Corporation as a principal research scientist in structural biology and biophysics. He left the company in 2004 to set up a research group at the Structural Genomics Consortium at Oxford University (SGC). From 2008 to 2015 he was a Professor of Structural Biology at the Nuffield Department of Clinical Medicine (NDM) at Oxford University (UK) and between 2012 and 2015 he was the Director for Chemical Biology at the Target Discovery Institute (TDI). He joined Frankfurt University (Germany) in 2015 as a Professor of Pharmaceutical Chemistry. He still remains associated to the SGC as a visiting Professor at Oxford University where he still run a research group. His research interests are the rational design of selective inhibitors that target protein kinases as well as protein interactions modules that function as reader domains of the epigenetic code.
Rational design of highly selective chemical probes for validation of novel drug targets
The development of highly selective inhibitors, also called chemical probes, is largely facilitated by large scale structural biology efforts focused on human protein families. In my group we currently working on mainly two target families: Bromodomains (BRDs), evolutionary conserved protein interaction modules that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks as well as protein kinases, a large family that has been extensively explored for the development of drugs. For the bromodomain family we have developed now a comprehensive set of chemical probes spanning all families of this protein family. For protein kinases we are particularly interested developing allosteric inhibitors. I will present examples for the structure based design of chemical probes for both protein families and will demonstrate how the now available inhibitors led to the development of new drug candidates and the validation of novel targets.