CONFORMATION AND DYNAMICS OF POLYSACCHARIDES

本课题采用物理化学的方法， 能量优先构象的平衡分布 碳水化合物聚合物和低聚物以及 这些分子从一种构象转变为另一种构象。 寡糖和多糖在生物学中起着重要的作用， 细胞识别、信号传导和粘附的过程。细菌 例如，荚膜多糖经常引起免疫反应， 在宿主生物体的反应，因此，有潜在的用途 生产针对病原体的疫苗。的能力 碳水化合物大分子结构和构象的多样性 使它们成为存储和表达 生物细胞表面的生物信息。全 要理解这些过程，就需要通过以下方式对过程进行评价： 糖的特定一级序列表达其构象 偏好，稳定优选构象的相互作用， 以及这些大分子从 分子中各种分子形状之间的一种构象与另一种构象 均衡分布 在这个项目中，几种结构简单的葡萄糖聚合物， 通过核磁共振弛豫和动态流变学研究， 它们在纳秒和微秒时间尺度上的运动速率。这些 实验由理论分析补充， 在分子基础上解释可观察到的动态特性。等 研究探索了分子内运动的基本过程， 当碳水化合物配体与蛋白质受体相互作用时发生。的 两种分子中多股螺旋结构及其稳定性 微生物多糖的种类是使用这样的 核磁共振光谱，电子和扫描探针显微镜， 光散射、扫描量热法和构象建模。这些 研究旨在阐明溶剂的性质和强度- 调节碳水化合物-碳水化合物相互作用， 水介质中的碳水化合物构象。这种碳水化合物-碳水化合物 相互作用也可能涉及某些生物识别 流程.

This project uses the methods of physical chemistry to investigate the equilibrium distribution of energetically preferred conformations of carbohydrate polymers and oligomers and the rates and mechanisms by which these molecules pass from one conformation to another. Oligo- and polysaccharides play an important part in the biological processes of cellular recognition, signaling, and adhesion. Bacterial capsular polysaccharides, for example, frequently elicit an immune response in the host organism and, hence, have potential uses in the production of vaccines against pathogenic organisms. The capacity of carbohydrate macromolecules for diversity of structure and conformation makes them ideal candidates for roles in the storage and expression of biological information at the surfaces of biological cells. A full understanding of these processes demands a appreciation of the process by which a particular primary sequence of sugars expresses its conformational preferences, the interactions which stabilize the preferred conformations, and the processes and pathways by which these large molecules pass from one conformation to another among the various molecular shapes in the equilibrium distribution. In this project several structurally simple polymers of glucose are investigated by means of NMR relaxation and dynamic rheology to probe their rates of motion on the nanosecond and microsecond time scales. These experiments are complemented by a theoretical analysis designed to interpret the observable dynamic properties on a molecular basis. Such studies probe the fundamental processes of intramolecular motion that may occur as a carbohydrate ligand interacts with a protein receptor. The structure and stability of multiple-stranded helical structures in two classes of microbial polysaccharides are investigated using such techniques as NMR spectroscopy, electron and scanning probe microscopy, light scattering, scanning calorimetry, and conformational modeling. These studies are designed to elucidate the nature and strength of the solvent- modulated carbohydrate-carbohydrate interactions that determine carbohydrate conformation in aqueous media. Such carbohydrate-carbohydrate interactions may also be involved in certain biological recognition processes.