Multivalent Well-Defined A,B-Alternating Polymers

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DESCRIPTION (provided by applicant): Multivalent lectin-carbohydrate interactions play an essential role in regulating physiological processes ranging from normal immune response to cancer proliferation and metastasis. Chemists have been contributing to the field of glycobiology by providing the tools, in the form of neoglycoconjugates, to aid in understanding the mechanism of these interactions. Multi-ligand polymers with a high avidity and selectivity for specific lectins will not only act as probes for binding these proteins, but also as potential therapeutics for diagnosis and treatment of diseases. While polymers have advantages such as a high valency and flexibility, synthesizing well-defined neoglycopolymers, with a known spacing and presentation of the saccharide ligands, is a challenge. This research proposal describes the synthesis of well-defined A,B-alternating polymers, bearing mannopyranoside ligands, using ring-opening-insertion-metathesispolymerization (ROIMP). The distance between the saccharide ligands will be controlled by synthesizing monomer spacers of varying length and rigidity. The binding of these polymers to concanavalin A, as a model system, to determine the optimum polymer backbone for binding the lectin with a high avidity.