SBIR TOPIC321:CHEMICALLY DEFINED GLYCAN LIBRARIES FOR REFERENCE STANDARDS AND GLY

SBIR 主题 321：参考标准品和 GLY 的化学定义聚糖库

• 批准号: 8758448
• 负责人: QINGFENG PAN
• 金额: $ 29.96万
• 依托单位: OMICRON BIOCHEMICALS, 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/8758448
• 关键词: Address; Bacterial Infections; Binding; Biochemical; Biological Assay; Biological Process; Cell surface; Cells; Chemicals; Commercial Sectors; Data; Development; Epitopes; High Pressure Liquid Chromatography; Immune response; Investigation; Knowledge; Libraries; Lipids; Mannose; Mass Spectrum Analysis; Molecular; Oligosaccharides; Parents; Phase; Polysaccharides; Process; Proteins; Protocols documentation; Reference Standards; Route; Sampling; Scheme; Shipping; Ships; Small Business Innovation Research Grant; Specificity; Structure; Time; Translations; Trisaccharides; Work; carbohydrate binding protein; enzyme substrate; experience; phase 2 study; polypeptide

Cell-surface oligosaccharides appended to proteins and lipids are key binding epitopes in many critical biological processes, including bacterial infection, cell development and the immune response. Understanding these processes at the molecular level requires access to a wide range of oligosaccharides of known structure to support investigations of enzyme substrate binding and specificity, to screen for carbohydrate binding proteins, and to develop assays for enzymic activity. These oligosaccharides are currently unavailable in the commercial sector, thus impeding progress in this field. To address this deficiency, the proposed project focuses on the synthesis of oligosaccharides derived from the parent high-mannose oligosaccharide (14-mer) that is transferred en-bloc to polypeptides during translation. Twenty-eight (28) high-mannose oligosaccharides ranging in size from tri- to hexa-saccharides will be prepared. Chemical routes will be used to synthesize each oligosaccharide in 0.2 mg or greater quantities and in high purity, as determined by NMR, highresolution mass spectrometry, and high-pressure liquid chromatography. Samples of each oligosaccharide, along with pertinent analytical data, will be packaged and shipped to the NCI for use in the construction of glycan arrays to screen for carbohydrate binding proteins, and for other biochemical or biomedical applications. This Phase I project will develop robust synthetic protocols that will be used in subsequent Phase II studies where the chemical space will be extended beyond hexasaccharides. These latter syntheses will be difficult to conduct without the knowledge, experience and technical know-how gained from the proposed Phase I work.

附加到蛋白质和脂质上的细胞表面寡糖是许多关键的关键结合表位 生物过程，包括细菌感染、细胞发育和免疫反应。 在分子水平上理解这些过程需要获得广泛的知识 已知结构的寡糖支持酶底物结合的研究和 特异性，筛选碳水化合物结合蛋白，并开发酶活性测定方法。 这些寡糖目前无法在商业领域获得，从而阻碍了这方面的进展 这个领域。为了解决这一缺陷，拟议的项目重点关注寡糖的合成 源自母体高甘露糖寡糖（14 聚体），整体转移至 翻译过程中的多肽。二十八 (28) 种高甘露糖寡糖，大小范围为 将制备三糖至六糖。化学路线将用于合成每种 低聚糖含量为 0.2 毫克或更多，且纯度高（通过 NMR、高分辨率测定） 质谱法和高压液相色谱法。各样本 寡糖以及相关分析数据将被包装并运送到 NCI 以用于 构建聚糖阵列以筛选碳水化合物结合蛋白和其他生化蛋白 或生物医学应用。该第一阶段项目将开发强大的合成方案 用于随后的第二阶段研究，其中化学空间将扩展到六糖之外。 如果没有知识、经验和技术，后面的合成将很难进行 从拟议的第一阶段工作中获得的专业知识。