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.
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