The oligosaccharide moieties of glycolipids and glycoproteins represent a diverse set of structures hypothesized to play roles in membrane surface reception, differentiation, and stabilization. They are also important markers for normal and abnormal cell growth, and are known targets for bacterial and viral infection. Yet, structural characterization of oligosaccharides at membrane surfaces has lagged behind that of other biomolecules; in part, through the lack of suitable analytical methodology. It is the broad objective of this proposal to develop this methodology and explore application to oligosaccharides important in membrane function. The methods involve both two dimensional 1H nuclear magnetic resonance (NMR) studies of oligosaccharides in solution, and 2H NMR studies of oligosaccharides oriented at membrane surfaces. An important aspect of the method development is integration of collected data with molecular modeling programs and development of computer assisted strategies for structural analysis. Oligosaccharides of direct interest are those found attached to gangliosides found in the membranes of the central nervous system. Studies will be directed at the ways in which ion binding and surface attachment influence preferred conformations of these molecules.
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