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Microarrays of Synthetic Heparin Oligosaccharides

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Heparin-like glycosaminoglycans (HLGAGs) play a key role in regulating the biological activity ofseveral proteins in the coagulation cascade along with many other processes of biomedical importance includinggrowth factor interactions, virus entry, and angiogenesis. However, the relationship between structure and activity of HLGAGs is still very poorly understood due to the complexity and heterogeneity of these polymers. A better understanding of heparin-protein interactions will create an opportunity for the discovery of novel therapeutic interventions for a variety of disease states. Carbohydrate microarrays are promising tools to aid in the discovery of oligosaccharides moieties necessary for carbohydrate-binding protein recognition. Here, we propose the novel preparation of microarrays of synthetic heparin oligosacharides (from solution and solid phase synthesis). First, the linker chemistry will be developed in order to attach the heparin molecules to a chip surface.This strategy will be compatible with the protecting-group manipulations required for the synthesis of HLGAGs. Several approaches will be examined to immobilize the synthetic molecules depending on the type of linker used. After developing the adequate technique for attachment, arrays equipped with a set of covalently immobilized heparin oligosaccharides will be prepared. To demonstrate the utility of such arrays, protein-carbohydrate interaction experiments will be carried out using heparin-binding proteins such as Fibroblast Growth Factors (FGF's). Microarrays will be analysed by using array readers and surface plasmon resonance.The development of automated solid phase methods for the synthesis of HLGAGs will be performed in order to enable the rapid generation of oligosaccharides in order to increase the complexity and diversity of heparin microarrays.

Wissenschaftliches Gebiet (EuroSciVoc)

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Aufforderung zur Vorschlagseinreichung

FP6-2002-MOBILITY-5
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

EIF - Marie Curie actions-Intra-European Fellowships

Koordinator

SWISS FEDERAL INSTITUTE OF TECHNOLOGY ZURICH (EIDGENOSSISCHE TECHNISCHE HOCHSCHULE ZURICH)
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