SYNTHESIS OF CARBOHYDRATE IMMUNOSTIMULATING AGENTS

碳水化合物免疫刺激剂的合成

• 批准号: 2741895
• 负责人: David Y Gin
• 金额: $ 23.64万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2741895
• 关键词: chemical synthesis; glycosylation; immunoconjugates; immunomodulators; oligosaccharides; technology /technique development

A research program devoted to the development of a new, direct dehydrative glycosylation method for the synthesis of complex oligosaccharides and glycoconjugates is proposed. The method involves in situ activation of the hemiacetal hydroxyl of a glycosyl donor with electrophilic, activated sulfoxide reagents, allowing for single step glycosylations with 1- hydroxyl glycosyl donors. Investigations into the score, mechanism, and catalytic potential of this new reaction should lead to a powerful and versatile stereoselective glycosylation reaction that can be applied to the synthesis of natural and non-natural oligosaccharides of biological utility. The application of the proposed dehydrative glycosidic coupling method to polymer-supported iterative oligosaccharide synthesis will be investigated. Successful development of this strategy should allow for single-step coupling iterations on the polymer support for the efficient construction of oligoscaccharides. Direct application of this glycosylation method for the synthesis of bioactive complex oligosaccharides is also proposed. Emphasis is directed toward the synthesis of immunostimulating agents, including: (1) the powerful adjuvant QS-21A; and (2) bioconjugatable oligosaccharides of the tumor gangliosides 9-O-acetyl-GD3 and N-glycoylyl-GM3 for potential use as subunit antigens in cancer vaccine development. The full development of this carbohydrate synthesis research program should greatly facilitate the use of these and other synthetic oligosaccharides of immunologic diagnosis and vaccine therapies.

一项研究计划，致力于开发新的直接脱水 糖基化方法用于合成复杂的寡糖和 提出了糖缀合物。该方法涉及原位激活 用亲电的糖基供体的半羟基羟基激活 亚氧化试剂，允许单步糖基化1- 羟基糖基供体。调查得分，机制和 这种新反应的催化潜力应导致强大的和 多才多艺的立体选择性糖基化反应可以应用于 生物学天然和非天然寡糖的合成 公用事业。提议的脱水糖苷耦合的应用 聚合物支持的迭代寡糖合成方法将是 调查。该策略的成功制定应允许 在聚合物支持上的单步耦合迭代以提高效率 寡糖的结构。 直接应用这种糖基化方法用于合成 还提出了生物活性复合寡糖。重点是指导的 朝着合成免疫刺激剂，包括：（1） 强大的辅助QS-21A； （2）可生物缀合的寡糖 肿瘤神经节9-O-乙酰基-GD3和N-聚糖L-GM3潜在用作 癌症疫苗发育中的亚基抗原。全面发展 该碳水化合物合成研究计划应大大促进 免疫诊断的这些和其他合成寡糖的使用 和疫苗疗法。