QUALITY CONTROL OF STUDIES OF OLIGOSACCHARIDE CHEMICAL ENZYMATIC SYNTHESIS

低聚糖化学酶法合成研究的质量控制

• 批准号: 6123303
• 负责人: DAVID Adam ZOPF
• 金额: --
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6123303
• 关键词: biomedical resource; plants; technology /technique

Oligosaccharides that block the adherence of bacteria to epithelial cells in vitro-lacto-N-neotetraose (LNnT) and its alpha 2-1,3- and alpha 2-6-sialylated derivatives were tested for their abilities to attenuate the course of pneumococcal pneumonia and to prevent colonization of thenasopharynx in animal models. Intratracheal administration of these agents concurrently with bacteria dramatically decreased pneumococcal load in the lungs of rabbits and conferred protection from bacteremia. Several oligosaccharides were prepared by a combination of chemical andenzymatic synthesis. The samples ameliorated pneumonia and bacteremia when given therapeutically 24 h after infection was established. When administered intranasally, neoglycoconjugates of the active oligosaccharides prevented colonization of the nasopharynx of infant rats. In addition to in-vitro anti-adherence properties, LNnT acted directly on cultured lung epithelial cell lines to induce changes such that pneumococcal adherence was prevented for prolonged periods. These activities have encourage continued development of oligosaccharides as a class of potentially preventive and therapeutic agents for infectious diseases. The work with the MS Resource is to carefully check the products synthesized for sequence and linkage. Additional concern for the compounds prepared is that we have some assessment for purity.

寡聚体阻止细菌粘附于 体外上皮细胞-乳糖-N-新四糖（LNnT）及其α 测试了2- 1，3-和α 2-6-唾液酸化衍生物的 减弱肺炎球菌性肺炎病程的能力， 防止动物模型中鼻咽部的定植。 这些药物的肠内给药与 细菌显着减少了肺部的肺炎球菌负荷 兔，并赋予保护从菌血症。 几 低聚糖是通过化学组合制备的 和酶促合成。 这些样品改善了肺炎， 感染后24小时给予治疗时， 确立了习 当鼻内给药时， 活性寡糖阻止鼻咽的定植 的幼鼠。 除了体外抗粘附特性之外， LNnT直接作用于培养的肺上皮细胞系， 这些变化使得肺炎球菌的粘附被长期阻止， 时期 这些活动鼓励了 低聚糖作为一类潜在的预防和治疗 传染病病原体。 MS资源的工作是 仔细检查合成产物的序列和连接。 对所制备的化合物的额外关注是，我们有一些 纯度评估。