|My Research Interest in RESIST|
As a part of the RESIST consortium, we will embark on the identification and multiparameter optimisation of inihibitors targeting DNA polymerase accessory proteins involved in replication of Kaposi’s sarcoma-associated herpesvirus. This underexplored antiviral drug target holds the potential to deliver new therapeutic options for herpesviral disease.
Our endeavour will rely on homology modeling and docking studies as well as ligand-based approaches. Biological studies in collaboration with the Schulz group as well as early in vitro profiling of pharmacological properties will guide the design and synthesis of optimized derivatives. A photo-cross-linking probe will enable target validation and would also reveal the exact binding site and thereby facilitate optimisation.
Anna Hirsch about her scientific work
Prof. Dr. Anna K. H. Hirsch – Curriculum Vitae
Undergraduate and Postgraduate Training
Academic and Research Posts
Awards and Prizes
C. Kaya, I. Walter, S. Yahiaoui, A. Sikandar, A. Alhayek, J. Konstantinović, A. M. Kany, J. Haupenthal, J. Köhnke, R. W. Hartmann et al., Substrate-Inspired Fragment Merging and Growing Affords Efficacious LasB Inhibitors, Angew. Chem. Int. Ed. 2021, DOI: 10.1002/anie.202112295.
R. P. Jumde, M. Guardigni, R. M. Gierse, A. Alhayek, D. Zhu, Z. Hamed, S: Johannsen, W. A. M. Elgaher, J. Haupenthal, A. K. H. Hirsch, Hit-Optimization Using Target-Directed Dynamic Combinatorial Chemistry: Development of Inhibitors of the Anti-Infective Target 1-Deoxy-D-Xylulose-5-Phosphate Synthase. Chem. Sci. 2021, in print.
C. Schütz, D.-K. Ho, M. M. Hamed, A. S. Abdelsamie, T. Röhrig, C. Herr, A. M. Kany, K. Rox, S. Schmelz, L. Siebenbürger, M. Wirth, C. Börger, S. Yahiaoui, R. Bals, A. Scrima, W. Blankenfeldt, J. C. Horstmann, R. Christmann, X. Murgia, M. Koch, A. Berwanger, B. Loretz, A. K. H. Hirsch, R. W. Hartmann, C.-M. Lehr, M. Empting, Adv. Sci. 2021, DOI: 10.1002/advs.202004369.
A. Axer, R. P. Jumde, S. Adam, A. Faust, M. Schäfers, M. Fobker, J. Koehnke, A. K. H. Hirsch, R. Gilmour, Enhancing glycan stability via site-selective fluorination: modulating substrate orientation by molecular design. Chem. Sci. 2021, 12, 1286–1294.
J. Konstantinović, S. Yahiaoui, A. Alhayek, J. Haupenthal, E. Schönauer, A. Andreas, A. Kany, R. Mueller, J. Köhnke, F. Berger, M. Bischoff, R. Hartmann, H. Brandstetter, A. K. H. Hirsch*, N -Aryl-3-mercaptosuccinimides as Antivirulence Agents Targeting Pseudomonas aeruginosa Elastase and Clostridium Collagenases. J. Med. Chem. 2020, DOI: 10.1021/acs.jmedchem.0c00584.
F. Mancini, M. Y. Unver, W. Elgaher, V. R. Jumde, A. Alhayek, P. Lukat, J. Herrmann, M. D. Witte, M. Köck, W. Blankenfeldt, R. Müller, A. K. H. Hirsch, Protein‐Templated Hit Identification via an Ugi Four‐Component Reaction. Chem. Eur. J. 2020, 26, 14585–14593.
S. Elangovan, A. Afanasenko, J. Haupenthal, Z. Sun, Y. Liu, A. K. H. Hirsch, K. Barta, From wood to tetrahydro-2-benzazepines in three waste-free steps: modular synthesis of biologically active lignin-derived scaffolds. ACS Central Science 2019, 5, 1707–1716.
M. Mondal, N. Radeva, H. Fanlo-Virgós, S. Otto, G. Klebe, A. K. H. Hirsch, Fragment-Linking and -Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry. Angew. Chem. Int. Ed. 2016, 55, 9422–9426.
M. Mondal, A. K. H. Hirsch, Dynamic combinatorial chemistry: a tool to facilitate the identification of inhibitors for protein targets. Chem. Soc. Rev. 2015, 44, 2455–2488.
M. Mondal, N. Radeva, H. Köster, A. Park, C. Potamitis, M. Zervou, G. Klebe, A. K. H. Hirsch, Structure-based design of inhibitors of the aspartic protease endothiapepsin by exploiting dynamic combinatorial chemistry. Angew. Chem. Int. Ed. 2014, 53, 3259–3263.