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Probing Molecular Recognition of the Avian and Human Influenza Virus (GlycoFluP)
Start date: 01 Mar 2009, End date: 31 Oct 2009 PROJECT  FINISHED 

The presence of carbohydrate structures on the surface of proteins has been estimated to occur in more than 50% of eukaryotic cells, and is linked to several biological events such as cell signalling regulation, cellular differentiation and immune response. Of the three classes of biooligomers, oligosaccharides have proven to be the most difficult to synthesize. Studies concerning the structure and function of oligonucleotides and peptides have greatly benefited from the feasibility of conducting their assembly on polymeric supports. In order to simplify the labor-intensive solution phase synthesis of carbohydrates, assembly of such compounds in an automated fashion on solid support is particularly desirable. Well-defined, synthetic carbohydrates not only constitute excellent research tools to investigate the structure and function of these biopolymers, but also hold great promise as potential therapeutic agents or vaccines against tumors and infectious diseases. Proposed is a program targeted at the synthesis of sialylated oligosaccharides that serve as receptors of avian and human influenza virus. Like other viruses, influenza viruses use interactions between a viral surface protein and well-defined cell surface oligosaccharides to initiate infection. Herein, we propose to prepare sialyl pentasaccharides by automated solid phase synthesis. The resulting complex carbohydrate structures will be attached to microarray slides that will be further subjected to binding experiments with different influenza virus hemagglutinin proteins. These glycan arrays will serve as molecular tools to understand important recognition and signal transduction processes of the infection mechanism by the influenza virus. The results obtained from these binding tests have the potential to create novel carbohydrate-based diagnostics and therapeutics for the influenza virus.
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