CONFORMATION AND DYNAMICS OF POLYSACCHARIDES

该项目旨在探索两国之间的基本关系 化学结构与分子构象和动力学 碳水化合物大分子。这些分布广泛的化合物是 所有生命系统的基本结构和能量储存部件。 它们的功能在真核细胞表面得到越来越多的认识。 其中，凭借它们的拓扑和构象能力 多样性，它们负责存储和表达 控制血型等现象的生物信息， 凝血链的调节、同种异体移植的接受性或 排斥、生长因子的接受和调节与细胞-细胞 认可度和粘合度。细菌被膜多糖在体内的作用 这些生物作为保护壳，控制着水的活动 细胞外表面和细胞的粘附性。这 胞外多糖在许多情况下都含有抗原决定簇 病原菌和无细胞样本被用作疫苗。 化学结构和大分子构象的问题是 使用计算机建模和定量相结合的方法 稀溶液性质的实验表征。因为 重点放在高聚合物上，它们必须表现出构象。 可变性即使当它们采用相对有序的螺旋构象时， 在计算机建模中必须使用统计力学的方法 在数量上和概念上准确地联系在 化学结构和可观察到的物理性质。可观察到的 感兴趣的特征是用最少的近似值计算的特征 从统计学理论出发。重点是全球构象特征 可通过光散射和流体力学测量获得，并可在当地 可通过适当的核磁共振测量获得的构象特征。 这些系统的动态和平衡性质都是在 调查。用~(13)C核磁共振弛豫测量来探索 构象运动的频谱，这些观测结果是 使用逼真的计算机以详细的分子术语进行解释 低聚糖水溶液的分子动力学模拟。

This project is designed to explore fundamental relationships between the chemical structure and the molecular conformation and dynamics of carbohydrate macromolecules. These widely distributed compounds are essential structural and energy storage components of all living systems. Their function is increasingly recognized at eukaryotic cell surfaces where, by virtue of their capacity for topological and conformational diversity, they are responsible for the storage and expression of biological information that governs such phenomena as blood type, regulation of the blood coagulation chain, allograft acceptance or rejection, growth factor reception and regulation, and cell-cell recognition and adhesion. Bacterial capsular polysaccharides function in these organisms as a protective shell and govern the activity of water at the external cell surface and the adhesive properties of the cell. This extracellular polysaccharide contains an antigenic determinant in many pathogenic bacteria, and cell-free samples are used as vaccines. The question of chemical structure and macromolecular conformation is approached using a combination of computer modeling and quantitative experimental characterization of the dilute solution properties. Because the emphasis is on high polymers, which necessarily exhibit conformational variability even when they adopt relatively ordered helical conformations, the methods of statistical mechanics must be used in the computer modeling to make a quantitative and conceptually accurate connection between chemical structure and observable physical properties. Observable characteristics of interest are those computed with fewest approximations from the statistical theory. Emphasis is on global conformational features obtainable from light scattering and hydrodynamic measurements and on local conformational features accessible from appropriate NMR measurements. Dynamic as well as equilibrium properties of these systems are under investigation. 13C NMR relaxation measurements are used to probe the frequency spectrum of conformational motions, and these observations are interpreted in detailed molecular terms using realistic computer simulations of the molecular dynamics of aqueous oligosaccharides.