MULTIVALENT PROTEIN CARBOHYDRATE INTERACTIONS

University Of Wisconsin Madison, Madison WI

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Abstract

DESCRIPTION: The overall objectives of this research project are to elucidate the role of multivalent binding in biological processes mediated by protein-saccharide interactions, to develop new methods to synthesize multivalent saccharide derivatives, and to generate multivalent saccharide derivatives with significant biological activity and medicinal functions. The carbohydrate-binding proteins to be studied range from structurally well-characterized systems to those in which the carbohydrate-binding site has not yet been definitively identified. The former group is composed of a series of mannose-binding proteins, which form defined oligomers and bind multivalent saccharide ligands (including Con A, serum mannose-binding protein and the liver mannose-binding protein). The wealth of structural information on these proteins makes them excellent systems in which to study structure/function relationships for multivalent saccharide ligands. The selectins, a family of proteins that mediates the tethering and rolling of leucocytes and lymphocytes along the vascular endothelium, comprise the second set. Several high affinity physiological ligands that bind the selectins present multiple carbohydrate determinants to the proteins; however the molecular bases of these high affinity interactions are unknown. The tools and information gained from investigating multidentate interactions with the mannose-binding proteins will be applied to the study of the selectins.