Multivalent Well-Defined A,B-Alternating Polymers

描述(由申请人提供)：多价凝集素-碳水化合物相互作用在调节从正常免疫反应到癌症增殖和转移的各种生理过程中发挥着重要作用。化学家们一直在为糖生物学领域做出贡献，他们提供了新的糖偶联物形式的工具，以帮助理解这些相互作用的机制。具有高亲和力和对特定凝集素选择性的多配体聚合物不仅可以作为结合这些蛋白质的探针，而且可以作为潜在的治疗药物用于疾病的诊断和治疗。虽然聚合物具有高价态和柔性等优点，但合成定义明确、糖类配体具有已知间距和呈现形式的新糖共聚物是一个挑战。这项研究计划描述了使用ring-opening-insertion-metathesispolymerization(ROIMP)合成定义明确的A，B交替聚合物，含甘露糖苷配体。糖配体之间的距离将通过合成不同长度和刚性的单体间隔物来控制。将这些聚合物与刀豆球蛋白A结合，作为模型体系，确定与凝集素结合的最佳聚合物骨架，具有高亲和力。

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.