Techniques

Targets

Teaching

 

 

 
   

Techniques

  • Synthesis of inhibitors
    • Lead structure-driven, mechanism-based, de novo

  • In vitro assay development
    • Fluorescence, fluorescence polarization, time-resolved fluorescence, AlphascreenR, FRET, luciferase, antibody-based assays, coupled assays
    • Synthesis and application of small molecule deacetylase substrates

  • Expression and purification of recombinant enzymes; nuclear extracts
    • currently: hSIRT1, 2 and 3, PCAF; HDACs from extracts

  • Application of assay techniques to in vivo material (hit validation)
    • Cell culture, blood, tissue samples
    • Protein acetylation, methylation; enzymatic activity (acetylation)

  • In vitro screening (approx. 7000 compounds from external suppliers)

  • In silico screening (collaboration with Prof. Dr. Wolfgang Sippl, Halle)


Targets (Inhibitor synthesis and screening)

  • Zinc-dependent histone deacetylases (HDACs)
    • Recent focus on subtype selectivity (esp. HDAC6)

  • NAD+-dependent histone deacetylases (Sirtuins)
    • Inhibitors based on focussed library and virtual screening
    • Selectivity studies with other NAD+-dependent enzymes

  • Histon acetyltransferases

  • Histone arginine and lysine methyltransferases
    • In-silico screening of large databases (Wolfgang Sippl, Halle)
    • Functional activity in reporter gene assays (R. Schüle, Freiburg)
    • Selectivity testing

  • Histone demethylases
    • FAD-dependent lysine-specific demethylase 1 (LSD1)
    • Iron(II)- and α-ketoglutarate-dependent JumonjiC histone demethylases

  • Early ADME tests (serum protein binding) based on fluorescence polarization

  • Numerous collaborations for cellular/animal activity (oncology, neuroscience)


Teaching

  • Group seminars
  • Lecture series "Assay Development"
   
   
   
   
 

 

 

 
     
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