NMR INVESTIGATIONS OF CELL SURFACE OLIGOSACCHARIDES

超出所提供的空间。一类新的核磁共振（NMR）实验被应用于细胞表面发生的低聚糖-蛋白质相互作用的结构和动态方面的表征。这些相互作用经常介导细胞-细胞接触，这对于宿主防御入侵生物，控制细胞的分化和激活，以及在炎症反应等事件中细胞的募集是重要的。在这些相互作用中，设计能够模仿或与自然参与者竞争的药剂对于对抗疾病非常重要。但是，这些试剂的合理设计只能通过对关键相互作用如何发生的充分的分子水平描述来进行。这个项目的长期目标是提供这种分子水平的描述。具体的方法是为了提供低聚糖结构和动力学的比较，在整个范围内的相互作用发生的环境；游离于溶液中，与膜结合，与蛋白质结合。利用可观测物的方向依赖性和距离依赖性的核磁共振方法非常适合这些研究。测试这种新方法是研究的关键组成部分。选择用于应用和测试的主要系统是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 -乙酰氨基葡萄糖胺端配体，以及选择素的碳水化合物识别结构域及其唾液-刘易斯相关配体。这两个系统的异常功能与当前的健康问题有关。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. 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. PERFORMANCE SITE ========================================Section End===========================================