METHODS FOR AUTOMATED SYNTHESES OF OLIGOSACCHARIDES AND LECTIN TAGS

低聚糖和凝集素标签的自动合成方法

• 批准号: 8137977
• 负责人: NICOLA L. B. POHL
• 金额: $ 28.48万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8137977
• 关键词: Affinity; Caenorhabditis elegans; Carbohydrates; Cell surface; Chemicals; Cross-Linking Reagents; Glucans; Glucosides; Glycosaminoglycans; Goals; Lectin; Mannans; Mannosides; Mass Spectrum Analysis; Methods; Nematoda; Oligosaccharides; Phase; Polysaccharides; Proteins; Proteomics; Route; S Phase; Solid; Solutions; Structure; Surface; Uronic Acids; base; carbohydrate binding protein; pathogen; pathogenic bacteria; public health relevance; response; sugar; tool

DESCRIPTION (provided by applicant): Carbohydrates are key to understanding and ultimately modulating host-pathogen interactions, but the study of these interactions has been hampered by access to well-defined glycan structures. The overall goals of this project, in response to RFA-GM-09-005 "Expanding the Chemical Space of Carbohydrates," are to develop quick routes to several key glycan building blocks, develop methods for the automated solution-phase synthesis of biologically important structures that contain not only common but also particularly difficult glycosidic linkages, and to develop a new tool using these synthetic glycans to identify protein partners of oligosaccharides on, for example, the surface of pathogenic bacteria. The specific aims of the proposed project are to: 1) develop methods for the automated syntheses of beta-glucosides and one of the most challenging glycosidic linkages-beta-mannosides-and apply these methods to the automated syntheses of fungally-associated glucans and mannans; 2) develop methods for the automated synthesis of the highly branched sugars found on the cell surface of the nematode C. elegans that are key to infectivity by various bacterial pathogens; 3) develop methods for the automated synthesis of uronic acid-containing repeating oligosaccharides and apply these methods to the synthesis of certain bacterial capsular polysaccharides and glycosaminoglycans; and 4) develop a new solid-phase-based cross-linking reagent that can incorporate these glycan products of the automated synthesis platform to identify carbohydrate binding proteins by mass spectrometry. PUBLIC HEALTH RELEVANCE: Carbohydrates are key to host-pathogen interactions, but their study has been limited because pure oligosaccharides are hard to obtain. The overall goals of this project, in response to RFA- GM-09-005 "Expanding the Chemical Space of Carbohydrates," are to develop quick routes to several key carbohydrate building blocks, develop methods for the automated solution-phase synthesis of biologically important structures that contain not only common but also particularly difficult glycosidic linkages, and to develop a new tool using these synthetic glycans to identify protein partners of oligosaccharides.

描述（由申请人提供）：碳水化合物是理解和最终调节宿主 - 病原体相互作用的关键，但是对这些相互作用的研究受到了获得明确定义的聚糖结构的障碍。该项目的总体目标是针对RFA-GM-09-005“扩展碳水化合物的化学空间”，是为了将快速途径开发到几个关键的聚糖构件，开发用于自动化溶液相综合的生物学上重要结构的方法，这些结构不仅包含常见的常见，还可以识别这些新工具，并使用这些新工具来识别这些合成的杂物，并构成合成的构成，寡糖上的寡糖，例如致病细菌的表面。拟议项目的具体目的是：1）开发用于β-葡萄糖苷自动合成的方法，以及最具挑战性的糖苷链接之一 - β-甘露糖苷之一，并将这些方法应用于真菌相关的葡萄糖和曼纳斯的自动合成器； 2）开发方法来自动合成在线虫C.秀丽隐杆线虫的细胞表面上发现的高度分支糖，这是各种细菌病原体感染性的关键； 3）开发了含有尿酸的重复寡糖的自动合成的方法，并将这些方法应用于某些细菌囊囊多糖和糖胺聚糖的合成； 4）开发一种新的基于固相的交联试剂，该试剂可以结合自动合成平台的这些聚糖产物，以通过质谱法鉴定碳水化合物结合蛋白。 公共卫生相关性：碳水化合物是宿主 - 病原体相互作用的关键，但是他们的研究受到限制，因为纯寡糖很难获得。 The overall goals of this project, in response to RFA- GM-09-005 "Expanding the Chemical Space of Carbohydrates," are to develop quick routes to several key carbohydrate building blocks, develop methods for the automated solution-phase synthesis of biologically important structures that contain not only common but also particularly difficult glycosidic linkages, and to develop a new tool using these synthetic glycans to identify protein partners of寡糖。