CHEMOENZYMATIC SYNTHESIS OF HEPARIN SULFATE OLIGOSACCARIDES

硫酸肝素低聚糖的化学酶法合成

• 批准号: 8758469
• 负责人: QUIN SHI
• 金额: $ 29.94万
• 依托单位: GLYCAN THERAPEUTICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-12 至 2014-06-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8758469
• 关键词: 2-cyclopentyl-5-(5-isoquinolylsulfonyl)-6-nitro-1H-benzo(D)imidazole; Affinity; Anions; Antithrombins; Binding; Collection; Contractor; Contracts; Disaccharides; Elements; Exhibits; Glucosamine; Glucosamine Sulfate; Glucuronic Acids; Goals; Heparin; Heparitin Sulfate; High Pressure Liquid Chromatography; Iduronic Acid; Inorganic Sulfates; Libraries; Link; Mass Spectrum Analysis; Methods; National Institute of General Medical Sciences; Oligosaccharides; Pattern; Polysaccharides; Preparation; Sampling; Small Business Innovation Research Grant; Therapeutic; Unspecified or Sulfate Ion Sulfates; chemical synthesis; compound 17; cost effective; good laboratory practice; innovation; response; sulfation

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.

本应用程序的目的是合成结构均匀的硫酸肝素（HS）文库