CARBOHYDRATE AND GLYCOPROTEIN INTERACTIONS WITH LECTINS

DESCRIPTION: (provided by applicant): the oligosaccharide chains of glycoproteins and glycolipids of normal and transformed cells have been shown to be receptors in a variety of biological processes, including cellular recognition, adhesion, apoptosis, differentiation and oncogenic transformation. Many of these biological effects are due to the interaction of glycoconjugate receptors with lectins which are carbohydrate binding proteins. The multivalent binding properties of lectins often results in cross-linking and aggregation of cell surface glycoconjugate receptors and concomitant signal transduction effects. Molecular and structural studies have shown that certain lectins form homogeneous cross-linked complexes with specific multivalent oligosaccharides and glycoproteins, even in the presence of mixtures of the molecules. Recent x-ray crystallographic studies have demonstrated the formation of unique crystalline 2- and 3-dimensional cross-linked lattices between lectins and a series of multivalent carbohydrates. Moe recently it has been observed that several specific glycoprotein receptors on the surface of human T cells undergo separation and selective clustering by the binding and cross-linking of galectin-1, an endogenous dimeric lectin, resulting in cell death. The galectin-1 induced separation andselective clustering of different counter receptors which are associated with phosphatase or kinase activities was modeled using our molecular studies of lectin-carbohydrate cross-linking interactions. These and other observations suggest that the selective cross-linking properties of galectin-1 and other members of the galectin family are important in their biological activities. The goal of this proposal is to determine the fine carbohydrate binding specificities, cross-linking and physical properties of galectins and related lectins in order to understand their structure-activity properties in normal and transformed cells.