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反应到癌症增殖和转移的生理过程中发挥重要作用。化学家通过提供新糖缀合物形式的工具来帮助理解这些相互作用的机制，为糖生物学领域做出了贡献。对特定凝集素具有高亲合力和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，而且可以作为诊断和治疗疾病的潜在疗法。虽然聚合物具有高化合价和灵活性等优点，但合成具有已知的糖配体间距和呈现形式的明确的新糖聚合物是一个挑战。该研究计划描述了使用开环插入复分解聚合 (ROIMP) 合成明确的 A,B-交替聚合物，带有吡喃甘露糖苷配体。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基来控制。这些聚合物与刀豆球蛋白 A 的结合作为模型系统，以确定以高亲合力结合凝集素的最佳聚合物主链。