Synthesis of Carbohydrate Immunostimulating Agents

碳水化合物免疫刺激剂的合成

• 批准号: 6845359
• 负责人: David Y Gin
• 金额: $ 30.94万
• 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 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6845359
• 关键词: chemical conjugate; chemical synthesis; drug design /synthesis /production; glycosylation; immunomodulators; oligosaccharides; tumor antigens

DESCRIPTION: (provided by applicant) A research program devoted to the development of new methods for the synthesis of complex oligosaccharides and glycoconjugates is proposed. The methods involve the development of new reagents for glycosidic bond formation, including sulfoxide-mediated dehydrative glycosylation, sulfide-mediated dehydrative glycosylation, 2-hydroxyglycosylation with glycals, and 2-amidoglycosylation with glycals. All of these methods involve novel reagents and reaction pathways for dehydrative coupling, oxygen transfer, and nitrogen transfer. Investigations into the scope and mechanism of these new reactions should lead to a series of powerful glycosylation methods that can be applied to the synthesis of natural and non-natural oligosaccharides of biological utility. Direct application of these glycosylation methods for the synthesis of bioactive complex oligosaccharides is also proposed. In this research program, emphasis is directed toward our synthetic efforts in the synthesis of immunostimulating agents including: (1) the powerful adjuvant QS-2 1 A; and (2) bioconjugatable oligosaccharides of the tumor gangliosides N-glycolyl-GM3 and Sle a 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 for immunologic diagnosis and vaccine therapies.

描述：（由申请人提供）专门针对该研究的研究计划 开发新方法，用于合成复杂的寡糖和 提出了糖缀合物。这些方法涉及新的开发 糖苷键形成的试剂，包括硫化介导的试剂 脱水糖基化，硫化物介导的脱水糖基化， 用糖基化2-羟基糖基化，并用糖基化2-氨基糖基化。全部 这些方法涉及脱水的新试剂和反应途径 耦合，氧转移和氮转移。调查范围 这些新反应的机制应导致一系列强大的 可以应用于自然和自然合成的糖基化方法 生物效用的非天然寡糖。 直接应用这些糖基化方法用于合成 还提出了生物活性复合寡糖。在此研究计划中 重点是指我们合成的合成努力 免疫刺激剂，包括：（1）强大的辅助QS-2 1 a； （2） 肿瘤神经节苷脂N-糖苷-GM3和 SLE A用于在癌症疫苗开发中作为亚基抗原的潜在用途。这 该碳水化合物合成研究计划的全面发展应大大开发 促进这些和其他合成寡糖的使用 免疫学诊断和疫苗疗法。