en
Michael Gütschow
© Uni Bonn
Prof. Dr. Michael Gütschow

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Affiliations
  • Pharmazeutisches Institut
Research topics
  • protease inhibition
  • PROTACs
  • activity-based probes
Based on investigations on the biochemistry of the protease-inhibitor interaction and on the analysis of detailed inhibition kinetics, we are designing and synthesizing tailored inhibitors for therapeutically relevant proteases, including human cysteine cathepsins, involved in tumor progression, and the main protease of SARS-CoV-2, a cysteine protease. We equipped such synthetic inhibitors with reporter groups to assemble activity-based probes as valuable tool compounds to study target enzymes in a pathophysiological context. Proteolysis targeting chimeras (PROTACs) are bifunctional small molecules, which simultaneously bind a target protein and an E3 ubiquitin ligase. We are developing PROTACs, e.g. for the self-directed ubiquitination and degradation of cereblon or the degradation of cyclin-dependent kinases, thus significantly contributing to this pioneering new modality in drug discovery.
Selected publications

Breidenbach J, Lemke C, Pillaiyar T, Schäkel L, Al Hamwi G, Diett M, Gedschold R, Geiger N, Lopez V, Mirza S, Namasivayam V, Schiedel AC, Sylvester K, Thimm D, Vielmuth C, Vu LP, Zyulina M, Bodem J, Gütschow M*, Müller CE* (2021) Targeting the main protease of SARS-CoV-2: From the establishment of high throughput screening to the design of tailored inhibitors. Angew Chem Int Ed 60:10423-10429.

Steinebach C, Ng YL. Sosič I, Lee CS, Chen S, Lindner S, Vu LP, Bricelj A, Haschemi R, Monschke M, Steinwarz E, Wagner KG, Bendas G, Luo J, Gütschow M*, Krönke J* (2020) Systematic exploration of different E3 ubiquitin ligases: An approach towards potent and selective CDK6 degraders. Chem Sci 11:3474-3486.

Häußler D, Schulz-Fincke AC, Beckmann AM, Keils A, Gilberg E, Mangold M, Bajorath J, Stirnberg M, Steinmetzer T, Gütschow M (2017) A fluorescent-labeled phosphono bisbenzguanidine as activity-based probe for matriptase. Chem. Eur. J. 23:5205-5209.

Löser R, Frizler M, Schilling K, Gütschow M (2008) Azadipeptide nitriles - highly potent and proteolytically stable inhibitors of papain-like cysteine proteases. Angew Chem Int Ed 47:4331-4334.

Michael Gütschow
© Uni Bonn
Prof. Dr. Michael Gütschow

Website

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