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: 6478957
• 负责人: Stephen J. Lippard
• 金额: $ 5.36万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6478957
• 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.

母乳中含有复杂而广泛的低聚糖， 其中一些可以保护身体免受毒素和病原体的侵害 婴幼儿疾病和其他影响一般人群的疾病 人口，如艾滋病。要记录不同因素带来的影响 婴儿饮食，尿液和粪便中存在的低聚糖 人们正在比较母乳喂养的婴儿和配方奶喂养的婴儿。在更早的时候 在这个项目的阶段，我们已经分离了人类的单个组件 牛奶对观察到的腹泻有抑制作用 与大肠杆菌稳定毒素(ST)相关的研究 哺乳小鼠，人类ST活动的既定模型， 并已将该分子部分表征为一种小岩藻糖化 低聚糖，我们已指定为QV。我们目前正在工作 为了分离和充分鉴定QV的分子结构， 确定其抵御圣母细胞病毒的机制，并发展 牛奶中QV含量的一种分析方法。我们将测试 乳汁中QV水平与ST相关疾病的关系 育苗，合成QV，或寻找合适的替代天然 来源；并测试QV预防ST相关疾病的效果 在人类身上。因此，这个项目的总体方向是 根据临床观察(年内胃肠炎发病率较低 母乳喂养婴儿)来分离和鉴定一种特定的 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的建立及其意义 作用机制，产生大量的活性因子，以及 检测其预防人体胃肠炎的有效性 人口。这项工作不仅直接解决了 ST相关腹泻，但对其他人来说是一个潜在作用的榜样 母乳中腐烂病原体受体类似物的保护护理 来自肠道病原体的婴儿。