Among the more important roles of oligosaccharides is the mediation of interactions between a cell and its external environment. These mediations occur naturally in the course of cell differentiation, clearance of serum proteins, and modulation of cell activity by certain hormones. They also occur on invasion of cells by pathogens including viruses and bacteria. In most cases the mediation involves specific recognition of an oligosaccharide receptor by an oligosaccharide binding protein. Characterization of conformational properties of oligosaccharides under conditions which approximate the natural binding environment is therefore of importance to the understanding of interactions that occur at surfaces of cells and the design of drugs that can compete with these interactions. The general aims of this project are the development and application of methodology that can provide this characterization. The methods rely heavily on Nuclear Magnetic Resonance (NMR) data and a computer based analysis that can lead to descriptions of oligosaccharides in terms of conformational and motional models. The NMR data are collected both in solution and in magnetic field oriented arrays of lipid membranes. In both cases enrichment of specific sites with NMR active nuclei (13C, 15N, 2H) helps select data relevant to oligosaccharide interactions from the otherwise complex experimental systems. Applications are to glycolipids and to glycolipids bound to lectins and bacterial toxins. Because a key question relates to whether a protein binds to a conformer which dominates in solution, a conformer favored by membrane surface interactions, or a conformer induced by the protein itself, characterization of properties at all three levels is undertaken. Results on the simple models studied are expected to provide insight into interactions which occur in a variety of carbohydrate recognizing proteins.
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