CHEMOENZYMATIC SYNTHESIS OF HEPARIN SULFATE OLIGOSACCARIDES

本申请目的是合成结构均一的硫酸乙酰肝素(HS)文库 低聚糖，响应来自NCI的SBIR合同呼吁--“321化学定义的葡聚糖库”。葡聚糖 Treateutics是一家专门合成结构多样的HS寡糖的公司。该公司 是建立在一种创新的化学酶法合成多糖的基础上的。聚合物HS中含有二糖基团 与氨基葡萄糖连接的葡萄糖醛酸或艾杜糖醛酸的单位，带有磺基。化学合成 合成结构均一的HS寡糖是极其困难的。化学酶法还原 合成复杂性，提供了一种经济高效的方法来制备各种HS低聚糖。 使用此方法构建具有不同大小和硫化模式的24个寡糖的文库 方法。Libaray代表了在自然产生的HS中发现的基本结构元素。综合应为 在良好实验室规范(GLP)下进行，每种化合物的标准为3毫克，数量为 适用于核磁共振、质谱学结构分析和阴离子交换纯度分析 高效液相色谱分析。样品准备和交付的四个里程碑是 清楚地标出了。所有24种化合物(每种50微克)应送至NIGMS指定的筛查中心。

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.