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.
Phillips-University Marburg (3month), University Groningen (one month)
List of publications:
List of posters:
Novel active site and allosteric site binders identified for farnesyl pyrophosphate synthase of Trypanosoma cruzi. Petrick J, Muenzker L, Schleberger C, Nelson E, Clavel D, Cornaciu I, Marquez JA von Delft F, Klebe G, Marzinzik A, Jahnke W; New Frontiers in Structure-Based Drug Discovery, Sept. 23-25, 2019, Florence, Italy
The Power of Fragments: FBLD approach to investigate proteins structure. Magari F, Petrick J, Metz A, Wollenhaupt J, Huschmann F, Bertoletti N, Hassaan E, Glöckner S, Siefker C, Abazi N, Heine A, Weiss M, Jahnke W, Klebe G; New Frontiers in Structure-Based Drug Discovery, Sept. 23-25, 2019, Florence, Italy
Fragment-based drug discovery targeting Trypanosoma brucei FPPS: Discovery of new binding sites. Müenzker L, Petrick J, Schleberger C, Cornaciu I, Márquez JA, Klebe G, Marzinzik A, Jahnke W; New Frontiers in Structure-Based Drug Discovery, Sept. 23-25, 2019, Florence, Italy
Fragment-based discovery of novel active and allosteric site binders of T. brucei farnesyl pyrophosphate synthase. Muenzker L, Petrick J, Klebe G, Marzinzik K, Jahnke W; 7th RSC-BMCS Fragment-based Drug Discovery meeting, 24th – 26th March 2019, Cambridge, United Kingdom
Fragment-based discovery of novel active and allosteric site binders of T. brucei farnesyl pyrophosphate synthase. Muenzker L, Petrick J, Klebe G, Marzinzik K, Jahnke W; 3rd Integrative Structural Biology School, Institut Pasteur, July 16 - 21, 2018, Paris, France
Targeting Trypanosoma brucei FPPS by fragment-based drug discovery. Muenzker L, Petrick J, Klebe G, Marzinzik K, Jahnke W; 9th International Conference on Structural Biology, Sep 8 - 20, 2017, Zurich, Switzerland
Targeting FPPS of Trypanosoma cruzi by fragment-based drug discovery.Petrick J, Muenzker L, Klebe G, Marzinzik A, Jahnke W; Revolutions in Structural Biology: Celebrating the 100th Anniversary of Sir John Kendrew, EMBL Heidelberg, Nov 16/17 2017
List of presentations:
„Targeting FPPS of Trypanosoma cruzi by fragment-based drug discovery”, Revolutions in Structural Biology: Celebrating the 100th Anniversary of Sir John Kendrew, EMBL Heidelberg, 16 – 17 Nov 2017
“Novel active and allosteric site binders identified for FPPS of T. cruzi”, 5th Novalix conference: Biophysics in Drug discovery 2018, Boston, 13 - 15 June 2018
Targeting farnesyl pyrophosphate synthase of Trypanosoma cruzi by fragment-based lead discovery. (on hold)
Novartis Pharma AG & Phillips-Universität Marburg, 21 Sep 2019, Basel, Switzerland & Marburg, Germany
Novartis Pharma AG
Center for Proteomic Chemistry
Institutes for Biomedical Research