NMR INVESTIGATIONS OF CELL SURFACE OLIGOSACCHARIDES

细胞表面低聚糖的核磁共振研究

• 批准号: 6385526
• 负责人: JAMES H. PRESTEGARD
• 金额: $ 30.49万
• 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/6385526
• 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特性的表征 寡糖-蛋白质相互作用发生在细胞表面的方面。 这些相互作用经常介导细胞间的接触， 宿主对入侵生物的防御，以控制分化和 细胞的激活，以及在诸如炎症性疾病等事件中细胞的募集， 反应可以模仿或与自然参与者竞争的代理设计 在这些相互作用中的重要性是对抗疾病。但是，理性的设计 只有在足够的分子水平上， 关键交互如何发生的描述。本项目的长期目标 提供了分子水平的描述。具体做法是指 为了提供寡糖结构和动力学的比较， 发生相互作用的环境范围;游离于溶液中， 与细胞膜和蛋白质结合。NMR方法利用 观测量的方向依赖性和距离依赖性， 非常适合这些调查。对这种新方法的测试是一种 研究的重要组成部分。选择应用的主要系统， 检测的是C型凝集素及其碳水化合物配体。其中包括 甘露糖结合蛋白的碳水化合物识别结构域，其甘露糖或 N-乙酰葡糖胺封端的配体，和碳水化合物识别 结构域的选择素，其唾液酸-路易斯-x相关的配体。异常 这两个系统的功能都与当前的健康问题有关。