Francesca Magari




Philipps-University Marburg


Prof. Gerd Klebe (PUM), Dr. Wolfgang Jahnke (NOVA)

Research Topic:

Fragment-based approaches to block protein functions at the example of FarnesylPyrophosphate Synthase (FPPS) and other model proteases.

About the project:

FPPS is a key enzyme in the metabolic mevalonate pathway. This target protein is important to treat protozoan parasite diseases such as Chagas disease and Sleeping Sickness, which are caused by T.cruzi and T.brucei, respectively. Typical inhibitors for FPPS are bisphosphonates. Unfortunately, due to their poor pharmacokinetic properties, the known bisphosphonates should be replaced with new selective compounds having a different mechanism of action. A promising candidate is the regulation of the allosteric pocket.
Using a crystallography-oriented fragment-based lead discovery approach, new ligands can be generated by targeting allosteric binding pockets of FPPS.  The optimization and validation of the initial hits will be performed using MCR. By exploring the chemical space around the hits, it will be possible to determinate the structure-activity relationship. The activity and kinetic properties of the compounds will be evaluate using SPR and ITC.


Personal information:

Francesca graduated with a Master’s Degree in Pharmaceutical Chemistry and Technologies at the University of Cagliari in 2015. During her master’s thesis, she worked under the supervision of Prof. Dr. E.Maccioni in collaboration with Prof. Dr. Kikeli from the University of Ljubljana. Her project aimed at the synthesis of new compounds with antibacterial activity. During this period, she acquired knowledge in synthesis, purification, structural characterization, and the design of new compounds. From October 2015 to March 2016, she did an internship with Prof. Dr. Klebe from the Philipps University of Marburg. There she gained new research experience by learning the techniques of protein expression and purification, crystallization, and soaking. Since April 2016, she started her PhD project in the same research group.



Novartis GmbH (2 months), University Uppsala (3 months)


List of publications:

Establishing Trypanosoma cruzi farnesyl pyrophosphate synthase as a viable target for biosensor driven fragment based lead discovery. Opassi G, Nordström H, Lundin A, Napolitano V, Magari F, Dzus T, Klebe G, Danielson UH;   Protein Science 2019, accepted

Design and Synthesis of Bioisosteres of Acylhydrazones as Stable Inhibitors of the Aspartic Protease Endothiapepsin. Jumde VR, Mondal M, Gierse RM, Unver MY, Magari F, van Lier RCW, Heine A, Klebe G, Hirsch AKH; ChemMedChem 2018, 13, 2266 – 2270. DOI:10.1002/cmdc.201800446



List of posters:

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

Crystallographic Screening of 96 Fragment Library Using Thermolysin as a Model Protein.Magari F, Krimmer S, Heine A, Klebe G; 18th Annual Drug Discovery Summit, 2017

X-ray Crystallographic Screening of a 96-Fragment Library using Thermolysin as a Model for Metalloproteinases: PanDDA Analysis helps to Improve Density Maps and Increase Hit Rates. Magari F, Metz A, Heine A, Klebe G; Ninth Joint BER II and BESSY II User Meeting, Dec 13/14, 2017, Berlin, Germany


List of presentations: