Synthesis of Two Thiol-terminated Disaccharides and a Mannose-branched Glycodendrimer

The glycocalix, a complex structure of lipids and glycoproteins, forms the cellular surface of all cells and serves to mediate a variety of events such as cell–virus recognition, cell–cell recognition, immunological response, metastasis, and fertilization. Moreover, the glycocalix is specific for a particular species, cell type, and developmental status. Alterations in the glycocalix have been found in association with many pathological conditions such as cancer and tuberculosis. Investigation of the interactions between the glycocalix and its associated proteins will lead to a fundamental understanding of these important processes.

Multivalent interactions are characterized by the simultaneous binding of multiple ligands on one biological entity to multiple receptors on another. These interactions occur throughout biology and have a number of characteristics that monovalent interactions do not. In particular, multivalent interactions can be collectively much stronger than the corresponding monovalent interactions, and they can provide the basis for mechanisms of both agonizing and antagonizing biological interactions that are fundamentally different from those available in monovalent systems.

To study multivalent interactions between carbohydrates and proteins, three mannose-bearing samples have been synthesized. The first two samples are thiol-terminated disaccharides prepared from Schmidt glycosylation and subsequent thiol introduction; the third is a mannose-branched glycodendrimer with first-generation branching.

The samples obtained in this dissertation will be used as probes to study multivalent carbohydrate–protein interactions on a synthetic surface with nanoparticles.