GLYCOSAMINOGLYCANS D · Glycosaminoglycans and their oligosaccharides derivatives : new opportunities in drug discovery.

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Project objective

The Glycosaminoglycans are biological polymers, which plays key roles in numerous biological processes. Glycosaminoglycan is mainly represented by heparin, heparan sulfate, chondoitins ABC and hyaluronic acid. Their structural heterogeneity and complexity is mainly linked to their sulfation degree. From basic disaccharide repeating units to highly complex disaccharide arrangement in the heparin backbone, a world of infinite structural diversity and oligosaccharide sequence is encompassed. The most fascinating is undoubtedly heparin. Through a specific interaction with antithrombine III, this polysaccharide is able to inhibit proteases involved in coagulation cascade. However, heparin is also able to interact with many proteins and its now obvious that particular sequences mediates other biological process than haemostasis (i.e. angiogenesis). For example, heparin discrete domains promote or inhibit cells proliferation through FGFs interaction. Again, other parts of the macromolecule are able to inhibit so-called inflammatory processes. Our goal is to disconnect the different biological properties of heparin by synthesizing specific oligosaccharidic sequences. This concept is extended to the other GAGs like chondroitins. The postdoctoral fellows will have to address GAGs specific issues in hemi-synthesis / total synthesis in other to prepare the targeted oligosaccharides.

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Participants

• AVENTIS PHARMA RECHERCHE DEVELOPPEMENT S.A. · VITRY SUR SEINECoordinatorFrance

Links

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