epigenetic targets, drug design, computational chemistry, cheminformatics
Structural models of many human epigenetic targets. Homology models of parasite epigenetic targets, in house library of epigenetic inhibitors
Computational chemistry, drug design and discovery, compound synthesis
Collaborations outside COST
A-PARADDISE (EU FP7) target-based strategy for the development of novel drug leads against epigenetic targets in schistosomiasis, leishmaniasis, Chagas disease and malariafocusing on key histone modifying enzymes (HME), in particular those involved in acetylation/deacetylation and methylation/demethylation.
Short description of ongoing research projects
Virtual screening for epigenetic modulators.
Structure-based design of inhibitors for parasitic epigenetic targets.
Synthesis of novel anti-parasitic inhibitors.
- T. Heimburg, A. Chakrabarti, M. Marek, J. Lancelot, J. Melesina, D. Robaa, F. Erdmann, M. Schmidt, R. J. Pierce, C. Romier, M. Jung and W. Sippl. Structure-Based Design and Synthesis of Novel Inhibitors targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis. J. Med. Chem, 59, 2423-35, 2016.
- T. Rumpf, M. Schiedel, B. Karaman, C. Rössler, B. J. North, K. I. Ladwein, M. Gajer, C. Steegborn, D. A. Sinclair, M. Schutkowski,, W. Sippl, O. Einsle, M. Jung. Structural basis for selective inhibition of hSirt2 by ligand induced rearrangement of the active site. Nat. Comm. 6, 6263, 2015.
- S. Kannan, J. Melesina, A.-T. Hauser, A. Chakrabarti, T. Heimburg, K. Schmidtkunz, A. Walter, M. Marek, R. J. Pierce, C. Romier, M. Jung and W. Sippl. Discovery of Inhibitors of Schistosoma Mansoni HDAC8 by Combining Homology Modeling, Virtual Screening and In Vitro Validation. J Chem Inf Model 54, 3005-19, 2014.
- C. Roessler, T. Nowak, M. Pannek, M. Gertz, G. T.T. Nguyen, M. Scharfe, W. Sippl, C. Steegborn, M. Schutkowski. Chemical probing of the human Sirtuin 5 active site reveals its acyl specificity and peptide-based inhibitors. Angew Chem Int Ed Engl. 53,10728-32, 2014.
- I. Slynko, M. Scharfe, T. Rumpf, J. Eib, E. Metzger, R. Schüle, M. Jung, W. Sippl. Virtual Screening of PRK1 Inhibitors: Ensemble Docking, Rescoring Using Binding Free Energy Calculation and QSAR Model Development. J. Chem. Inf. Model. 54, 138–150, 2014.
Other activities of potential interest to others