SBIR PHASE I. TOPIC321:CHEMICALLY DEFINED GLYCAN LIBRARIES FOR REFERENCE STANDARD

SBIR 第一阶段。主题 321：参考标准的化学定义的聚糖文库

• 批准号: 8758478
• 负责人: HAI YU
• 金额: $ 29.84万
• 依托单位: GLYCOHUB, INC.
• 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/8758478
• 关键词: 2-cyclopentyl-5-(5-isoquinolylsulfonyl)-6-nitro-1H-benzo(D)imidazole; Biological Assay; Cancer Vaccines; Carbohydrates; Cell membrane; Complex; Data; Diagnostic; Event; Glycosphingolipids; Head; Health; Human; Libraries; Malignant Neoplasms; Mass Spectrum Analysis; NMR Spectroscopy; National Institute of General Medical Sciences; Phase; Polysaccharides; Production; Reference Standards; Resolution; Series; Sialic Acids; Small Business Innovation Research Grant; Structure; Testing; Therapeutic; Validation; base; cost; cost effective; design; molecular recognition; novel; screening

Glycosphingolipids are essential components of human plasma membrane. More than 300 glycosphingolipid glycans have been characterized. The glycans are directly involved in molecular recognition event. A number of cancer-associated glycosphingolipid glycans are being developed as cancer vaccines. Most glycosphingolipid glycans are not commercially available. The costs for a limited number of commercially available ones are extremely high. We have developed highly effective one-pot multienzyme (OPME) approaches for high-yield and cost-effective production of complex glycans. The OPME approaches will be used in generating a library of 60 structurally diverse glycosphingolipid glycans including those contain different naturally occurring sialic acid forms. Three specific aims are to synthesize 1) ganglio-series; 2) lacto- and neolacto-series; and 3) globo- and isoglobo-series glycosphingolipid glycans using our established high efficient OPME strategies. Each of the 60 compounds will be synthesized under GLP conditions in 10-50 mg scale, purified to >98% purity, and characterized by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). For all glycans synthesized (>98% purityL 50 micrograms of each will be sent to an NIGMS-designed screening center for validation testing, glycan microarray and other screening assays. These glycans are essential standards and invaluable probes for bioassays and biomedical applications.

鞘糖脂是人体细胞膜的重要组成部分。300多 已经表征了鞘糖脂聚糖。聚糖直接参与分子 识别事件。正在开发许多与癌症相关的鞘糖脂聚糖， 癌症疫苗大多数鞘糖脂聚糖不可商购。有限的成本 商业上可获得的数量非常高。我们开发了高效的一锅法 多酶（OPME）方法，用于高产率和成本效益的生产复合聚糖。的 OPME方法将用于产生60种结构不同的鞘糖脂聚糖库 包括含有不同天然唾液酸形式的那些。三个具体目标是 合成1）神经节系列; 2）乳糖和新乳糖系列; 3）球蛋白和异球蛋白系列 使用我们建立的高效OPME策略，分析鞘糖脂聚糖。每60个 化合物将在GLP条件下以10-50 mg规模合成，纯化至>98%纯度， 通过核磁共振光谱（NMR）和高分辨率质谱（MS）表征， 光谱法（HRMS）。对于合成的所有聚糖（纯度>98%），将每种50微克发送至 NIGMS设计的筛选中心，用于验证测试、聚糖微阵列和其他筛选 测定。这些聚糖是生物测定和生物医学的基本标准和宝贵的探针 应用.