Executive Summary : | Ligand-lectin interactions between cell surface bound oligosaccharides, glycoproteins, and glycolipids with exogenous lectins are responsible for various diseases, including viral and bacterial infections. The density-driven binding of cell surface bound carbohydrates with proteins is crucial for various immunological responses, including cell-cell communications and intracellular interactions. Understanding these interactions is essential for developing therapeutic regimes. However, molecular level delineation of these interactions remains limited. Multivalency, a concept that aims to uncover finer binding mechanisms, requires optimized ligand design through chemical and biochemical means. Identifying interaction efficacies through biochemical and biophysical methods is also necessary for therapeutic developments. The patterns of ligand-lectin interactions with cell surface carbohydrate ligands leading to acute cellular regulations are unclear. The involvement of multivalency phenomenon has become reasonably established, and a custom-designed multivalent ligand has the most potential to uncover finer details of these cellular regulation events. Addressing cellular functions through multivalency, specifically carbohydrate-protein interactions, is imminent and a continuing contemporary theme and therapeutic approach. This research proposal aims to address these approaches through the synthesis of well-defined multivalent ligands and studies using biochemical and biophysical techniques. The design of multivalent ligands on dendritic and polymeric scaffolds, densities, and topological presentations will be considered. Tight binding multivalent inhibitors will be developed to provide immunological, elevated, or depleted signaling responses by host cells. |