Post-translational methylations play central roles in epigenetic gene regulation, but there remain few synthetic agents that can help us to study or antagonize these pathways. Lysine methylations are turn-on switches for hundreds of distinct protein-protein interactions. We have been developing new approaches to making chemicals that can mimic, sense, or antagonize the lysine-methylation-driven biochemistry important to healthy and disease-linked cellular processes. We have created organic macrocycles that can recognize and bind to methylated sites on proteins, including examples that disrupt methylation-driven protein-protein interactions and others that can provide a readout of a protein’s post-translational modifications. We have also targeted a family of methyllysine reader proteins called chromodomains, having created antagonists of the epigenetic master controller Chromobox homolog 7 (CBX7) that are the first inhibitors of any chromodomain. We characterize all of our systems using a wide array of biochemical, biophysical, physical organic, and cell-based analytical techniques. In doing so we have both made useful tool compounds by design, and discovered molecules with completely unexpected properties.
Talk will be held by:
Prof. Dr. Fraser Hof, Canada Research Chair in Supramolecular and Medicinal Chemistry, Department of Chemistry, University of Victoria, CANADA
Prof. Dr. Werner Nau, Professor of Chemistry, Focus Area: Health - Life Sciences & Chemistry, Building Research III, Room 112 / Campus Ring 6 / 28759 Bremen / Germany,
Email: w.nau [at] jacobs-university.de - Tel: +49 421 200-3223 / Fax: +49 421 200-3102 - Link to Homepage: http://www.jacobs-university.de/ses/wnau