Entwicklung verbesserter Fosmidomycin-Derivate

• Antragsteller: Professor Dr. Martin Schlitzer
• Fachliche Zuordnung: Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
• Förderung: Förderung von 2002 bis 2007
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5401914

In the malaria parasite Plasmodium falciparum, isoprenoid are synthesised via the 1-deoxy-D-xylulose 5-phosphate (DOXP) pathway which is absent in humans. In a clinical proof-of-concept study fosmidomycin, an inhibitor of DOXP reductoisomerase (DXR), was demonstrated to possess potent antimalarial activity. However, fosmidomycin does not act selectively against DXR in malaria parasites but also inhibits the DXR in a variety of bacterial species. Therefore, new DXR inhibitors which are more specific for P. falciparum DXR need to be developed using a structure-based approach. The available crystal structure of E. coli DXR will be used to create a structural model of the highly homologous DXR from P. falciparum.

• DFG-Verfahren: Sachbeihilfen