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（根据摘要改编）：一种新的核磁共振 （NMR）实验用于结构和动态的表征 在细胞表面发生的寡糖蛋白相互作用的各个方面。 这些相互作用经常介导对细胞电池的接触，这对于 宿主防御入侵生物以控制分化和 细胞的激活，并在炎症等事件中募集细胞 回复。可以模仿或与自然参与者竞争的代理商的设计 在这些相互作用中，对于打击疾病很重要。但是，理性设计 这些药物只能以足够的分子水平进行 有关关键相互作用的发生的描述。这个项目的远距离目标 正在提供此分子级描述。具体方法是指 总体上提供寡糖结构和动力学的比较 相互作用发生的环境范围；在解决方案中免费 与膜结合，并与蛋白质结合。 NMR使用的方法 定向依赖性以及可观察到的距离依赖性是 独特地适合这些调查。这种新方法的测试是 研究的关键组成部分。选择用于应用的主要系统， 测试是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域，其甘露糖或 N-乙酰葡萄糖终止配体和碳水化合物识别 来自Selectin的结构域，其相关的Lewis-X与配体相关。异常 两种系统的功能都与当前的荒地关注有关。