Novartis Pharma AG
Dr. Wolfgang Jahnke (NOVA), Prof. Gerd Klebe (PUM)
Discovery of novel chemotypes for the treatment of trypanosomatid and apicomplexan protozoal infections.
About the project:
The aim of my PhD project is to identify inhibitors of a novel chemotype for the treatment of Chagas disease (CD) which is caused by the parasite T. cruzi. Bisphosphonates (Bps) can combat the flagellate but are non-effective on CD. The molecular target of BPs is farnesyl pyrophosphate synthase (FPPS), an enzyme in lipid biosynthesis and therefore critical for the survival of the flagellate. Seven years ago an allosteric non-bisphosphonate inhibitor was found by FBDD for human FPPS by Jahnke et al. The existence of a similar so-called allosteric pocket in T. cruzi FPPS became the trigger for a FBDD effort which is object of my work. This includes protein expression and purification, fragment screening and validation by NMR, as well as characterizing by other biophysical methods. Hits are analyzed by crystallography to obtain a protein-ligand structure. This will be the starting point for a medicinal chemistry campaign with the goal to turn a primary fragment hit into a tool compound.
Born in Hamburg and studied near the Baltic see, I graduated with a Master’s degree in Chemistry from the University of Rostock, Germany. For my PhD project in drug discovery I moved from the north of Germany to the very south to work at Novartis in Basel, Switzerland. Now I am located at the region where three countries meet in the heart of Europe, where I fell in love with the mountains and the good weather! Now not only cycling, but also hiking is one of my favorite free time activities.
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Novartis Pharma AG
Center for Proteomic Chemistry
Institutes for Biomedical Research