NMR INVESTIGATIONS OF CELL SURFACE OLIGOSACCHARIDES

描述(摘自摘要)：一类新的核磁共振 (核磁共振)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。 这些相互作用经常调节细胞与细胞之间的接触，这对 寄主对入侵生物的防御以控制分化和 细胞的激活，以及在炎症等事件中细胞的募集 回应。能够模仿自然参与者或与之竞争的代理的设计 在这些相互作用中对抗击疾病很重要。但是，理性的设计 这些药物只能在足够的分子水平上进行 对关键交互如何发生的描述。这个项目的长期目标是 正在提供这一分子水平的描述。具体的做法是指 从整体上比较低聚糖的结构和动力学 相互作用发生的环境范围；在溶液中自由， 与膜结合，与蛋白质结合。核磁共振方法利用 观测值的方位依赖关系和距离依赖关系 非常适合这些调查。对这种新方法的测试是一个 这项研究的关键组成部分。选择用于应用的主系统和 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及其甘露糖或 N-乙酰氨基葡萄糖终止配体和碳水化合物的识别 来自选择素的结构域，及其唾液酸路易斯-x相关配体。异常 这两个系统的功能都与当前的健康问题有关。

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.