Chemical synthesis of d-galactofuranosyl species providing new avenues for drug design in the treatment of chagas' disease

Lines connect the coordinator with its partners.

Project objective

Research objectives and content D-Galactofuranosyl residues occur in saccharides of glycocongugates found in parasites, such as those causing Chagas' Disease, but are not present in mammalian glycoconjugates. Inhibition of D-galactofuranose biosynthesis may therefore provide new therapeutic agents for the treatment of such diseases. The synthesis of a disaccharide containing D-galactofuranose and its stable C-disaccharide analogue will be developed. The key synthetic step will utilise a tethered radical coupling of two monosaccharides as developed by Sinay and allow stereoselective formation of the interglycosidic C-C linkage. These disaccharides will be tested as direct inhibitors of the biosynthesis of D-galactofuranose, but will also be attached to a carrier protein and used to raise specific antibodies against Chagas' Disease. Another aspect of the programme will focus on the synthesis of a stable C-linked analogue of UDP-galactofuranose, via a short series of known transformations This C-UDP-galactofuranose should directly inhibit the enzyme UDP-galactopyranose mutase, which has recently been studied by GlaxoWellcome and shown to be of central importance in the biosynthesis of galactofuranose. Training content (objective, benefit and expected impact) This project will provide: new experience in techniques of biochemistry (immunology and enzymology), an extended knowledge of carbohydrate chemistry and develop new practical skills in a broad range of modern synthetic methods. Links with industry / industrial relevance (22) Access to new therapeutic agents and a deeper understanding of galactofuranose biosynthesis should be of interest to GlaxoWellcome, given their recent studies on the mutase enzyme.

Original text from CORDIS.

Participants

• ECOLE NORMALE SUPERIEURE · PARISCoordinatorFrance

Links

• View on CORDIS