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Michael Gütschow
© Uni Bonn
Prof. Dr. rer. nat. Michael Gütschow
Faculty of Mathematics & Natural Sciences

Website

Affiliations
  • Pharmaceutical Institute, Department of Pharmaceutical and Medicinal Chemistry
Research topics
  • COVID-19 therapeutics
  • PROTACs
  • inhibitors of human cysteine & serine proteases
  • structure-activity relationships of biologically active heterocycles
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, Voget R, Si Y, Hingst A, Claff T, Sylvester K, Wolf V, Krasniqi V, Useini A, Sträter N, Ogura Y, Kawaguchi A, Müller CE, Gütschow M; Macrocyclic Azapeptide Nitriles: Structure-Based Discovery of Potent SARS-CoV-2 Main Protease Inhibitors as Antiviral Drugs. J Med Chem. 2024;67(11):8757-8790. doi: 10.1021/acs.jmedchem.4c00053. 

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 L P, Zyulina M, Bodem J, Gütschow M, Müller CE;  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. 2021;60(18):10423-9. doi: 10.1002/anie.202016961.

Steinebach C, Ng YLD, Sosič I, Lee CS, Chen S, Vu LPV, Lindner S, Bricelj A, Haschemi R, Monschke M, Steinwarz E, Wagner KG, Bendas G, Luo J, Gütschow M,. Krönke J; Systematic exploration of different E3 ubiquitin ligases: an approach towards potent and selective CDK6 degraders, Chem Sci. 2020;11(13):3474-6.

Löser R, Frizler M, Schilling K, Gütschow M; Azadipeptide nitriles: highly potent and proteolytically stable inhibitors of papain-like cysteine proteases. Angew Chem Int Ed. 2008;47(23):4331-4. doi: 10.1002/anie.200705858.

Meusel M, Ambrozak A, Hecker TK, Gütschow M; The aminobarbituric acid-hydantoin rearrangement. J Org Chem. 2003;68(12):4684-92. doi: 10.1021/jo020761f.

Michael Gütschow
© Uni Bonn
Prof. Dr. rer. nat. Michael Gütschow
Faculty of Mathematics & Natural Sciences

Website

+49 228 73 2317

+49 228 73 2567

An der Immenburg 4

53121 Bonn