NMR INVESTIGATIONS OF CELL SURFACE OLIGOSACCHARIDES

细胞表面低聚糖的核磁共振研究

• 批准号: 2852348
• 负责人: JAMES H. PRESTEGARD
• 金额: $ 29.99万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2852348
• 关键词: carbohydrate receptor; carbohydrate structure; cell membrane; intermolecular interaction; lectin; liquid crystal; mannose; membrane structure; method development; nuclear magnetic resonance spectroscopy; oligosaccharides; protein structure; selectins; solutions; structural biology

DESCRIPTION (Adapted from abstract): A new class of nuclear magnetic resonance (NMR) experiments is applied to the characterization of structural and dynamic aspects of oligosaccharide-protein interactions that occur at cell surfaces. These interactions frequently mediate cell-cell contacts that are important to host defense against invading organisms to control of differentiation and activation of cells, and to recruitment of cells in events such as inflammatory response. Design of agents that can mimic or compete with natural participants in these interactions is important in combating disease. But, rational design of these agents can only be undertaken with adequate molecular level descriptions of how key interactions occur. The long range goal of this project is providing this molecular level description. The specific approach is meant to provide a comparison of oligosaccharide structure and dynamics, in the whole range of environments over which the interactions occur; free in solution, bound to membrane, and bonded to protein. NMR approaches that utilize orientational dependence as well as distance dependence of observables are uniquely suited to these investigations. Testing of this new methodology is a key component of the research. The primary systems selected for application and testing are C-type lectins and their carbohydrate ligands. These include the carbohydrate recognition domain of mannose binding protein, with its mannose or N-acetylglucosamine terminated ligands, and the carbohydrate recognition domains from a selectin, with its sialy-Lewis-x related ligands. Abnormal function of both systems relate to current heath concerns.

描述（改编自摘要）：一类新的核磁共振 （NMR）实验应用于结构和动态表征 发生在细胞表面的寡糖-蛋白质相互作用的各个方面。 这些相互作用经常介导细胞与细胞的接触，这对于 宿主防御入侵生物体以控制分化和 细胞的激活，以及在炎症等事件中招募细胞 回复。设计可以模仿自然参与者或与自然参与者竞争的代理 这些相互作用对于对抗疾病很重要。但是，合理的设计 这些药物只能在足够的分子水平上进行 关键交互如何发生的描述。该项目的长期目标 正在提供这种分子水平的描述。具体做法的意思是 提供寡糖结构和动力学的比较 相互作用发生的环境范围；溶液中游离， 与膜结合，并与蛋白质结合。 NMR 方法利用 可观测量的方向依赖性和距离依赖性是 非常适合这些调查。对这种新方法的测试是 研究的关键组成部分。为应用程序选择的主要系统和 测试的是C型凝集素及其碳水化合物配体。这些包括 甘露糖结合蛋白的碳水化合物识别结构域，及其甘露糖或 N-乙酰氨基葡萄糖封端的配体和碳水化合物识别 来自选择素的结构域及其唾液酸-刘易斯-x相关配体。异常 两个系统的功能都与当前的健康问题有关。