CHEMOENZYMATIC SYNTHESIS OF HEPARIN SULFATE OLIGOSACCARIDES

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The goal of this application is to synthesize heparan sulfate (HS) library consisting of structurally homogeneous oligosaccharides, in response to a SBIR contract call from NCI-"321 Chemically Defined Glycan Libraries". Glycan Therapeutics is a company specializing in the synthesis of structurally diverse HS oligosaccharides. The company is built on an innovative chemoenzymatic method for Glycan synthesis. Polymeric HS contains the disacchariderepeating units of glucuronic or iduronic acid linked to glucosamine that carry sulfo groups. Chemical synthesis of structurally homogeneous HS oligosaccharides is extremely difficult. The chemoenzymatic method reduces synthetic complexity, providing a cost-effective approach to prepare a diverse collection of HS oligosaccharides. A library of 24 oligosaccharides with different sizes and sulfation patterns shall be constructed using this method. The libaray represents the basic structural elements found in naturally occurring HS. Synthesis shall be carried out under good laboratory practice (GLP) at a scale of 3 mg for each compound, which amount is sufficient for structural analysis by NMR and mass spectrometry as well as the purity analysis by anion-exchange high performance liquid chromatography (HPLC). Four milestones for sample preparations and deliveries are clearly marked. All 24 compounds (50 microgram each) shall be delivered to the NIGMS-designated screen center.