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Prof. Dr. Michael Gütschow

Universität Bonn
Pharmazeutisches Institut
Pharmazeutische Chemie I
An der Immenburg 4
D-53121 Bonn
Deutschland

Tel: +49 228 732317
Fax: +49 228 732567

guetschow@uni-bonn.de

 
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Forschung

  • Development of low-molecular inhibitors of proteases and esterases (with cysteine proteases, human serine proteases from leukocytes and mast cells, membrane-bound serine proteases as well as serine esterases as main target enzymes)

    obc_big

A gorge-spanning, high-affinity cholinesterase inhibitor to explore β-amyloid plaques (Elsinghorst, P.W. et al. Org. Biomol. Chem. 2009, 7, 3940-3946).


brunsvicamide b

Model of the cyanobacterial cyclic peptide brunsvicamide B bound to the active site of human leukocyte elastase (Sisay, M.T. et al. ChemMedChem 2009, 4, 1425-1429).


 Reik_Chem_Med_Chem_2
 

Synthesis and radiopharmacological characterization of a fluorine-18-labelled azadipeptide nitrile as PET-tracer for cathepsin imaging in vivo (Löser, R. et al. ChemMedChem 2013, 8, 1330-1344).   

 

Janus Inhibitors 3

A bisbenzamidine phosphonate as a Janus-faced inhibitor for trypsin-like serine proteases (Häußler, D. et al. ChemMedChem 2015, 10, 1641-1646).

     

  • Characterization of the key role of the membrane-bound type II transmembrane serine protease matriptase-2 in iron homeostasis; analysis of matriptase-2 activity regulation; identification of putative interaction partners of matriptase-2

    MTP2 

By cleaving hemojuveline (m-HJV), the bone morphogenetic protein (BMP) co-receptor, matriptase-2 downregulates SMAD signaling leading to suppressed hepcidin expression and increased iron plasma levels (for a review, see: Stirnberg, M. and Gütschow, M. Curr. Pharm. Des. 2013, 19, 1052-1061).


Coverpicture_2016_Häußler

Phosphono Bisbenzguanidines as Irreversible Dipeptidomimetic Inhibitors and Activity-Based Probes of Matriptase-2 (Häußler, D. et al. Chem. Eur. J. 2016).

 

 

Characterization of low-molecular weight ligands using active-site-mutated variants of matriptase-2 (Maurer, E. et al. ChemMedChem 2012).

 

 

  • Mechanism of the enzyme-inhibitor interactions, enzyme kinetics, e.g. analysis (UV/Vis spectroscopy, fluorescence, HPLC) of the reactions of enzymes with mechanism-based inhibitors and artificial substrates

 

cease1cease2 

Kinetics of the cholesterol esterase-catalyzed hydrolysis of 6,7-dihydro-2-dimethylamino-4H,5H-cyclopenta[4,5]thieno[2,3-d][1,3]oxazin-4-one. Left: Depletion of the compound is illustrated by monitoring UV/VIS-spectra at 10 min-intervals. Right: Hydrolysis of the compound was followed at 350 nm (Pietsch, M. and Gütschow, M. J. Med. Chem. 2005, 48, 8270-8288).

 

  • Development of synthetic inhibitors of angiogenesis and TNF-alpha production

    

  • Activity-based probes for proteases

    activity based probes

    An activity-based probe to chemically introduce the green fluorescence for the ex vivo imaging of human cysteine cathepsins (Frizler, M. et al. Org. Biomol. Chem. 2013, 11, 5913-5921.

     
  • Synthesis and structural elucidation of bioactive heterocycles, investigations on heterocyclizations, ring cleavages, trapping reactions.

 
Synthesis_2009_neu

Investigations on alternative ring closures and analysis of rotational barriers (Häcker, H. G. et al. Synthesis 2009, 1195-1203).


 pao

An access to biologically active aza-Freidinger lactams and E-locked analogs (Ottersbach, P. A. et al. Org. Lett. 2013, 15, 448-451). 

 

 

 sulfonylation_new

Regioselective sulfonylation and intramolecular N- to O-sulfonyl migration as verified by kinetic and crossover experiments (Mertens, M. D. et al. J. Org. Chem. 2013, 78, 8966-8979. 

 

  • Aminobarbituric acid-hydantoin rearrangements


    hydantoins 

    Formation of trisubstituted hydantoins (Meusel, M. et al. J. Org. Chem. 2003, 68, 4684-4692).
     

  • Structure-activity relationships of biologically active heterocycles and structural optimization using molecular modelling


cathepsin 

Docking of 2-(4-methylpiperazinyl)-4H-3,1-benzoxazin-4-one toward the active site of cathepsin G. (Gütschow, M. et al. Arch. Biochem. Biophys. 2002, 402, 180-191).


Structure-Based_Design_Trypsin-Like_Protease_Inhibitors_2015

Limiting the Number of Potential Binding Modes by Introducing Symmetry into Ligands: Structure-Based Design of Inhibitors for Trypsin-Like Serine Proteases (Furtmann, N. et al. Chem. Eur. J. 2016, 22, 610-625).

 

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