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Prof. Dr. Manfred Jung

Freiburg
Institute of Pharmaceutical Sciences

Albert-Ludwigs-Universität Freiburg

Albertstraße 25

79104 Freiburg

Programm

Exploitation of Oncogenic Mechanisms (EOM)

Übersicht

Our group focusses on the investigation of epigenetic pathways using chemical tools. We work on the medicinal chemistry of potential therapeutic agents, develop chemical tools to interrogate biological questions and biochemical assays for epigenetic inhibitor screening as well as methods of cellular target engagement analysis.
In medicinal chemistry, we follow different approaches to identify new hit structures which are then optimized in iterative bioguided cycles of synthesis and testing. Such approaches are mechanism-based, ligand driven and structure driven, also using virtual screening (in collaborations). Focussed library screening with enriched chemical libraries is also employed. Covered targets encompass histone deacetylases (HDACs and sirtuins), histone acetyltransferases, histone demethylases (LSD1 and JmJD-domain containing enzyms), histone methyltransferases and methyl-lysine binding proteins (e.g. Spindlin1).
We have assembled a focused epigenetic inhibitor library comprising 40 compounds covering all the major epigenetic target classes. This focused inhibitor set can be used in phenotypic or functional cellular models to generate new target dependence hypotheses. For chemical biology studies we work e.g. on biotinylated chemical probes for chemoproteomic approaches or fluorescence labelled inhibitors for cellular localization studies.
The development of biochemical screening assays focuses mainly on histone modifying enzymes but also involves protein-protein interactions of epigenetic reader proteins with client proteins, such as histones. We are also active in the expression and purification of target proteins. Available assays mostly use fluorescence based techniques (Fluorescence, fluorescence polarization, time-resolved fluorescence, AlphascreenR, FRET, luciferase, antibody-based assays, coupled assays) but we also employ biophysical techniques (Thermofluor-thermal stabilization, Biolayer interferometry). Cellular target engagement is studied using Western blotting and cellular thermal stabilization (CETSA).

Find out more on the website of the Manfred Jung group