Prof. Dr. Anna K. H. Hirsch participates in research project D1.

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

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Prof. Dr. Anna K. H. Hirsch – Curriculum Vitae

Current Position

  • As of 05/17 Head of department and full professor, Helmholtz Institute for Pharmaceutical Research Saarland and Saarland University, Saarbrücken, Germany

Undergraduate and Postgraduate Training

  • 2008–2010 Postdoctoral Fellow, Institut de Science et d’Ingénierie Supramoléculaires, France Prof. J.-M. Lehn: supramolecular and dynamic covalent chemistry

  • 2010–2015 Assistant professor of bio-organic chemistry, University of Groningen, NL

  • 2015–2017 Associate professor structure-based drug design, University of Groningen, NL

Academic and Research Posts

  • Since 2020: Member of the Council of the European Federation of Medicinal Chemistry

  • Since 2021: Member of the editorial board of ChemMedChem

  • Since 2020: Member of the technology development board at Helmholtz Centre for Infection Research

  • Since 2020 / 2021: Member of the Innovation Prize in Medicinal and Pharmaceutical Chemistry (GDCh and DPhG; since 2021) and Grohe Prize (GdCh; since 2020) juries

  • Since 2021:- Member of the programme board of the HZI

Awards and Prizes

  • 2018 ERC starting grant „NovAnI“

  • 2019 „NaPAnti“ (Development of natural product-based antibacterials targeting the sliding clamp DnaN) (BMBF, Federal Ministry of Education and Research)

  • 2020 ITN “MepAntI” (Exploiting the methylerythritol phosphate pathway as a source of drug targets for novel anti-infectives) (Horizon 2020; coordinator)

  • 2020 Indirect-acting small-molecule inhibitors of Elastase (LasB) for the treatment of P. aeruginosa lung infections (Carb-X)

Recommended Links

For further information about Prof. Dr. Anna K. H. Hirsch’s scientific work please check the following links:

Top-10 Publications

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.

Contact

  Prof. Dr. Anna K. H. Hirsch
Helmholtz Institute for Pharmaceutical Research Saarland and Saarland University
Saarbrücken

Germany

  +49 681988062100
anna.hirsch@
helmholtz-hips.de