NMR INVESTIGATIONS OF CELL SURFACE OLIGOSACCHARIDES

细胞表面低聚糖的核磁共振研究

• 批准号: 7228124
• 负责人: JAMES H. PRESTEGARD
• 金额: $ 35.59万
• 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 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7228124
• 关键词: Acetylglucosamine; Adoption; Binding; C-Type Lectins; Carbohydrates; Cell Communication; Cell surface; Cells; Chemicals; Class; Collection; Complex; Coupling; Data; Dependence; Detection; Development; Diffusion; Disease; Environment; Event; Glycolipids; Goals; Head; Health; Host Defense; Hydrogen Bonding; Individual; Inflammatory Response; Invaded; Investigation; Label; Lectin; Ligand Binding; Ligands; Lipids; Magic; Mannose; Mannose Binding Lectin; Maps; Measurement; Mediating; Membrane; Membrane Proteins; Methodology; Methods; Molecular; Motion; Nuclear Magnetic Resonance; Numbers; Oligosaccharides; Organism; Participant; Pliability; Property; Protein Binding; Proteins; Protons; Range; Reagent; Relative (related person); Relaxation; Research; Research Personnel; Residual state; Sampling; Selectins; Site; Solutions; Specificity; Structure; Surface; System; Techniques; Testing; Work; X-Ray Crystallography; barley lectin; base; data acquisition; design; improved; liquid crystal; magnetic field; nuclear Overhauser enhancement; programs; research study

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 contactsthat 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 reagents 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 bound 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 sialyl-Lewis" related ligands. Abnormal function of both systems relate to current health concerns.

将新的一类核磁共振（NMR）实验应用于表征 在细胞表面发生的寡糖蛋白相互作用的结构和动态方面。这些 相互作用经常介导细胞电池的接触，这对于防御防御很重要 生物体，控制细胞的分化和激活，以及在诸如事件中的细胞募集 炎症反应。可以模仿或与自然参与者竞争的代理商的设计 相互作用对于打击疾病很重要。但是，这些试剂的理性设计只能进行 有足够的分子水平描述关键相互作用的发生方式。远距离目标 项目提供了这种分子级别的描述。具体方法旨在提供 在整个环境范围内的寡糖结构和动力学的比较 发生相互作用；在溶液中免费，与膜结合并与蛋白质结合。 NMR接近这一点 利用定向依赖性以及可观察物的距离依赖性非常适合这些 调查。对这种新方法的测试是研究的关键组成部分。主要系统 选择用于应用和测试的是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，其甘露糖或N-乙酰葡萄糖胺 终止配体和来自Selectin的碳水化合物识别域，其siallyl-lewis相关 配体。两种系统的异常功能都与当前的健康问题有关。