BINDING OF HMG1 DOMAIN PROTEINS TO CISPLATINATED DOUBLE STRANDED DNA

HMG1 结构域蛋白与顺铂双链 DNA 的结合

• 批准号: 6206428
• 负责人: Stephen J. Lippard
• 金额: $ 0.75万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6206428
• 关键词: biomaterials; biomedical resource; carbohydrates; child (0-11); drug discovery /isolation; female; growth /development; health care; human tissue; male; mother /infant health care; structural biology

Human milk contains a complex and wide array of oligosaccharides, some of which protect against toxins and pathogens involved in diseases of infants and other diseases that strike the general population, such as AIDS. To document the effects from differences in infant diet, the oligosaccharides present in urine and feces from breast-fed and formula-fed infants are being compared. In an earlier phase of this program, we have isolated the single component of human milk responsible for the observed inhibition of the diarrhea associated with the stable toxin (ST) of Escherichia coli in the suckling mouse, an established model for ST activity in humans, andhave partially characterized this molecule as a small fucosylated oligosaccharide that we have designated QV. We are currently working to isolate and fully characterize the molecular structure of QV, determine the mechanism whereby it protects against ST.- and develop an analytical method for measuring QV levels in milk. We will test the relationship between QV levels in milk andST-related disease in the nursling, synthesize QV, or find suitable alternate natural sources; andtest the efficacy of QV in preventing ST-related disease in humans. Thus, the overall direction of this project is to move from a clinical observation (lower incidence of gastroenteritis in breastfed infants) to the isolation and characterization of a specific non-immunoglobulin human milk factor that inhibits ST-induced secretory diarrhea in the infant mouse model, to understanding its mechanism of action, producing large amounts of the active factor, and testing itsefficacy in preventing gastroenteritis irr a human population. This work not only directly addresses the problem of ST-related diarrhea, but is a model for a potential role for other putativepathogen receptor analogs from human milk that protect nursing infants from enteric pathogens.

人乳中含有复杂而广泛的低聚糖， 其中一些可以防止毒素和病原体， 婴儿的疾病和其他疾病， 人口，如艾滋病。 为了记录差异的影响， 婴儿饮食中，尿液和粪便中存在的低聚糖， 正在对母乳喂养和配方奶喂养的婴儿进行比较。 在较早的 在这个项目的第一阶段，我们已经分离出了人类的单一成分， 牛奶负责观察到的腹泻抑制 与大肠杆菌的稳定毒素（ST）相关， 乳鼠是人类ST活动的既定模型， 并已部分将该分子表征为小岩藻糖基化的 我们命名为QV的低聚糖。 我们目前正在 为了分离和充分表征QV的分子结构， 确定它保护免受ST的机制。和发展 用于测量牛奶中QV水平的分析方法。 我们将测试 牛奶中QV水平与ST相关疾病的关系 哺育，合成QV，或找到合适的替代天然 来源;并测试QV在预防ST相关疾病中的功效 在人类身上。 因此，本项目的总体方向是 根据临床观察（2010年胃肠炎发病率较低）， 母乳喂养的婴儿）的分离和表征的一个特定的 抑制ST诱导的非免疫球蛋白人乳因子 分泌性腹泻幼鼠模型，了解其 作用机制，产生大量的活性因子，和 测试其预防人类肠胃炎的功效 人口 这项工作不仅直接解决了 ST相关腹泻，但却是其他潜在作用的模型 母乳中假定的病原体受体类似物可保护哺乳 婴儿免受肠道病原体感染。