Objectif In recent years, the search for new lead molecules in pharmaceutical research has been radically altered by the introduction of combinatorial technologies. Our goal is to apply these techniques to the discovery of novel anticancer agents designed to act on a specific enzyme in the cell. This enzyme, termed Protein Farnesyl Transferase (PFTase), is implicated in the post-translational modification of proteins such as Ras, found mutated in approximately 30% of all human cancers. Compared to classical cytotoxic agents, PFTase inhibitors represent one of the few classes of anticancer agents that could constitute a real improvement in the cancer therapy. Indeed, these drugs are able to selectively target cancer cells while normal cells remain unaffected. Ras proteins required prenylation for activity and this transfer of a farnesyl group from farnesyl pyrophosphate (FPP) to a cysteine residue of Ras protein is catalyzed by PFTase. Two approaches are possible to inhibit this farnesylation. The first is to design compounds that mimic the terminal residue of the Ras protein (CAAX box) and the second is to design compounds that will compete with FPP. The efforts of our chemistry team have been mainly focused on the discovery of original PFTase inhibitors that mimic the CAAX box. The project of the Fellow will be to design compounds that will compete with FPP. This new approach will create a stimulating environment in that it will require numerous exchanges with other researchers. Champ scientifique medical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) FP5-HUMAN POTENTIAL - Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002) Thème(s) Data not available Appel à propositions Data not available Régime de financement BUR - Bursaries, grants, fellowships Coordinateur INSTITUT DE RECHERCHE PIERRE FABRE, S.A.S. Contribution de l’UE Aucune donnée Adresse Av. Jean Moulin 17 81106 CASTRES France Voir sur la carte Coût total Aucune donnée
