NMR INVESTIGATIONS OF CELL SURFACE OLIGOSACCHARIDES

一类新的核磁共振实验被应用于表征 发生在细胞表面的寡糖-蛋白质相互作用的结构和动态方面。这些 相互作用经常调节细胞间的接触，这对宿主防御入侵很重要 生物体，控制细胞的分化和激活，以及在诸如 炎症反应。能够模仿自然参与者或与之竞争的代理的设计 相互作用在抗击疾病方面很重要。但是，这些试剂的合理设计只能进行。 对关键相互作用是如何发生的进行了充分的分子水平描述。这样做的长期目标是 该项目正在提供这种分子水平的描述。该特定方法旨在提供一种 低聚糖结构和动力学的比较，在整个环境范围内 发生相互作用；在溶液中游离，与膜结合，与蛋白质结合。核磁共振接近于 利用可观测对象的方位相关性和距离相关性，特别适合于这些 调查。对这一新方法的测试是这项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。其中包括 甘露糖结合蛋白的糖识别域及其甘露糖或N-乙酰氨基葡萄糖 终止的配体和来自选择素的碳水化合物识别结构域，与其唾液酸基-刘易斯相关 配基。这两个系统的异常功能与当前的健康问题有关。

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.