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Synthesis of a new class of potent glycosidase inhibitors: analysis of their biological activities; synthesis of a library of gem-difluoro-carbaglycosides: exploration of sugar-protein interactions

Objective

This proposal aims to make a major contribution to the European Research Area and add value to the EU in specific ways. The host research group at l'Ecole Normale Superieure has developed a fruitful industrial partnership with Sanofi-Aventis that has led to the release of a new antithrombotic agent "Arixtra" on the market last year. This project will synthesise families of related molecules and test their biological activities. The fellowship will allow an exceptional young scientist to diversify his re search, work in a multidisciplinary field gaining new skills in biochemistry and carbohydrate chemistry as well as reinforcing his present skills in synthetic organic chemistry and spectroscopy.
These new skills will allow the fellow to reach a position of professional maturity and give him a multidisciplinary platform to begin a career as an EU academic. The project will synthesise several new families of biologically important sugar mimics based on azacycloheptene intermediates and gain access to novel in dolizidine and pyrrolizidine scaffolds through the use of more complex amines. This work will take advantage of the expertise in the Sinay Group and the synthetic skills of the fellow and will be carried out at l¿Ecole Normale Superieure. Biological evaluation of these new sugar mimics will be carried out in collaboration with Prof P. Vogel (Switzerland) and the active conformation of these molecules will be established in collaboration with Prof. J. Jimenez-Barbero (Madrid). A library of biologically important gem-difluoro-carba-sugar analogues will be generated using methodology developed in the Sinay group. These gem-difluoro-carba-sugars will be used to investigate sugar-protein interactions using NMR (19F) spectroscopy in collaboration with Prof. J. J imenez-Barbero (Madrid) and the biological activities of these sugar mimics will be evaluated in collaboration with Prof P. Vogel (Switzerland).

Call for proposal

FP6-2002-MOBILITY-5
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Coordinator

ECOLE NORMALE SUPERIEURE