Drug Design and Optimization

This group is located at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)

In order to combat the increasing number of resistant pathogens, the development of new anti-infective drugs is an important goal for pharmaceutical research. Efficient medications with novel modes-of-action to fight infectious diseases are urgently needed. Below, you may read more about the design, identification and optimisation of new drug candidates. This group is located at the Helmholtz Institute for Pharmaceutical research Saarland (HIPS). 

Leader

selected Publications Prof. Dr. Hirsch

Mondal, M., Radeva, N., Fanlo-Virgós, H., Otto, S., Klebe, G., Hirsch, A. K. H. (2016) Fragment-Linking and -Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry. Angew. Chem. Int. Ed., 55, 9422–9426.

Mondal, M., Hirsch, A. K. H. (2015) Dynamic Combinatorial Chemistry: a Tool to Facilitate the Identification of Inhibitors for Protein Targets. Chem. Soc. Rev., 44, 2455–2488.

Masini, T., Hirsch, A. K. H. (2014) Development of Inhibitors of the 2C-Methyl-D-erythritol 4-Phosphate (MEP) Pathway Enzymes as Potential Anti-Infective Agents. J. Med. Chem. 57, 9740–9763.

Masini, T., Kurz, J., Kroezen, B. S., Illarinov, B., Fischer, M., Griesinger, C., Hirsch, A. K. H. (2014) De novo structure-based design enabled by INPHARMA NMR spectroscopy. Chem. Sci. 5, 3543–3551.

Mondal, M., Radeva, N., Köster, H. Park, A., Potamitis, C., Zervou, M., Kebe, G., Hirsch, A. K. H. (2014) Structure-Based Design of Novel Inhibitors of the Aspartic Protease Endothiapepsin Exploiting Dynamic Combinatorial Chemistry. Angew. Chem. Int. Ed. 12, 3259–3263.

full list of publications

Selected Publications Prof. Dr. Hartmann

Lu, C., Maurer, C.K., Kirsch, B., Steinbach, A., Hartmann, R.W. (2014) Overcoming unexpected functional inversion of PqsR antagonist in Pseudomonas aeruginosa led to the first in vivo potent anti-virulence agent targeting pqs quorum sensing, Angewandte, 53, 1109 –1112

Storz, M.P., Brengel, C., Weidel, E.,  Hoffmann, M., Hollemeyer, K., Empting, M. Steinbach, A., Müller, R., Hartmann, R.W. (2013) Biochemical and biophysical analysis of a chiral PqsD inhibitor revealing tight-binding behavior and enantiomers with contrary thermodynamic signatures, ACS Chem. Biol., 8, 2794-2801

Sahner, H.J., Brengel, C.,  Storz, Groh, M., Plaza, A.P.,  Negri, M.,  Müller, R., Hartmann, R.W. (2013) Combining in silico and biophysical methods for the development of Pseudomonas aeruginosa quorum sensing inhibitors - an alternative approach for structure-based drug design, J. Med.Chem., 56, 8656-8664

Zender, M., Klein, T., Henn, C., Kirsch, B., Maurer, C.K., Kail, D., Ritter, C., Dolezal, O., Steinbach, A., Hartmann, R.W.(2013) Discovery and Biophysical Characterization of 2-Amino-Oxadiazoles as novel Antagonists of PqsR - an important regulator of Pseudomonas aeruginosa virulence, J. Med. Chem., 56, 6761−6774

Weidel, E., DeJong, J., Brengel, C., Storz, M., Braunshausen, A., Negri, M., Plaza, A., Steinbach, A., Müller, R., Hartmann, R. (2013) Structure Optimization of 2-Benzamidobenzoic acids as PqsD inhibitors for Pseudomonas aeruginosa infections and elucidation of binding mode by SPR, STD NMR and molecular docking, J. Med. Chem., 56, 6146−6155

Hüsecken, K., Negri, M., Fruth, M., Hartmann, R.W., Haupenthal, J. (2013) Peptide-based investigation of the Escherichia coli RNA polymerase σ70:core interface as target site, ACS Chem. Biol., 8, 758–766

Storz,M.P.; Maurer,C.K.; Zimmer,C.; Wagner,N.; Brengel,C.; De Jong,J.C.; Lucas,S.; Musken,M.; Häußler,Susanne; Steinbach,A.; Hartmann,Rolf W.;  (Jahr: 2012). Titel: Validation of PqsD as an Anti-biofilm Target in Pseudomonas aeruginosa by Development of Small-Molecule Inhibitors. Zeitschrift: Journal of the American Chemical Society

full list of publications

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Video

  • HIPS Infofilm (English)

    Resistance to antibiotics has become one of the major global challenges regarding infectious diseases. This is specifically the issue that is being tackled by the new Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS).

Audio Podcast

  • Kündigung für Biofilm-WGs – Pharmazeuten des HIPS stören BakteriengemeinschaftenBakterien haben einen ausgeprägten Gemeinschaftssinn und verschanzen sich gerne in schleimigen Biofilmen. Etwa 60 Prozent aller bakteriellen Infektionen lösen inzwischen Biofilme aus. Ein besonders geselliger Keim ist Pseudomonas aeruginosa. Er ist besonders für Mukoviszidose-Patienten gefährlich. Wissenschaftler am Helmholtz-Institut für Pharmazeutische Forschung Saarland suchen nach Wegen, seine Biofilme aufzulösen – damit Medikamente wirken können. Begleiten Sie Anke Steinbach in Ihre Labore...
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