Multivalent Well-Defined A,B-Alternating Polymers

多价明确定义的 A,B-交替聚合物

• 批准号: 6986132
• 负责人: Alshakim Nelson
• 金额: $ 0.57万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-07 至 2005-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6986132
• 关键词: carbohydrates; chemical synthesis; concanavalin A; glycolipids; glycoproteins; intermolecular interaction; lectin; ligands; polymerization; polymers; postdoctoral investigator; protein binding

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.

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应答到癌症增殖和转移的生理过程中发挥重要作用。化学家们一直在为糖生物学领域做出贡献，以新糖缀合物的形式提供工具，以帮助理解这些相互作用的机制。多配体聚合物对特异性凝集素具有高亲和力和选择性，不仅可以作为结合这些蛋白质的探针，而且还可以作为潜在的疾病诊断和治疗药物。虽然聚合物具有诸如高化合价和柔性的优点，但合成具有已知的糖配体的间距和呈现的明确定义的neoglycopolymers是一个挑战。本研究计划描述了使用开环插入易位聚合（ROIMP）合成定义明确的A，B-交替聚合物，带有甘露吡喃糖苷配体。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。结合这些聚合物的伴刀豆球蛋白A，作为一个模型系统，以确定最佳的聚合物骨架结合凝集素与高亲和力。