Paolo Mombelli   PhD Student Location: HCI G-328 Phone: +41-1-633 4167 e-mail:

Structure-Based Design and Synthesis of Inhibitors for IspE, an Enzyme of the Non-Mevalonate Pathway of Isoprenoid Biosynthesis

With more than one million deaths and over 500 millions clinical cases a year, malaria is the most important tropical disease. The emergence of multi-drug resistance of P. falciparum, the most dangerous parasite responsible for malaria, has increased the need of drugs with new mechanisms of action. The non-mevalonate pathway is exclusively used by many pathogens such as P. falciparum but not by humans for the biosynthesis of isoprenoids. Therefore, the enzymes in this pathway are promising candidates for the development of antimalarial drugs. The aim of this project is the de novo design and synthesis of new inhibitors against IspE (4-diphosphocytidyl-2C-methyl-D-erythritol kinase), the fourth enzyme of the pathway. The design will be done with the aid of MOLOC, a molecular modeling program developed by Hoffmann-La Roche in Basel.

Last update: May 2008