MODIFIED NUCLEOSIDE STRUCTURE FUNCTION RELATIONS TRNA

修饰核苷结构与 TRNA 的功能关系

• 批准号: 6120900
• 负责人: PAUL F AGRIS
• 金额: $ 0.1万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6120900
• 关键词: bacteria; biological products; biomedical resource; carbohydrates; infection; nuclear magnetic resonance spectroscopy; respiratory system

The biosynthesis of two cell-wall polymers, arabinogalactan and lipoarabinomannan, is to be studied with cell-free preparations of Mycobacterium smegmatis and M. Tuberculosis H37Ra. In the present phase of the project, chemical synthesis is being used to obtain nucleoside diphosphate derivatives of the pentose D-arabinose. The object is to test these derivatives as primary donors of D-arabinose residues in the biosynthetic process. The preferred synthetic procedure involves the glycosidation of D-arabinose to methyl a-D-arabinofuranoside, benzoylation of the glycoside to the 2,3,5-tribenzoate, and conversion of the benzoate into the protected glycosyl chloride and/or bromide. The glycosyl halides will then be treated with the tetrabutylammonium salts of uridine diphospate and guanosine diphosphate d-arabinofuranoses. Alternatively, tetrabutylammonium dibenzyl phosphate may be reacted with the protected arabinosyl chloride or bromide, and the product deprotected to give D-arabinofuranose 1-phosphate. Reaction of the 1-phosphate with the phosphormorpholidates of the nucleoside diphosphate of interest should give the corresponding nucleoside diphosphate arabinofuranoses. Since all or nearly all of the intermediates in the proposed syntheses, and two of the final products, have been described in the literature, operations can be monitored by examining the high resolution 1H NMR spectrum of each compound as it is obtained. For the final products 13C and 31P spectra may also be useful. Once the reliability of the syntheses is established with ordinary reagents, the preparation of radioactive samples will be undertaken, with 1-[14C]-D-arabinose as the labeled starting material.

两种细胞壁聚合物阿拉伯半乳聚糖和 脂阿拉伯甘露聚糖，将用无细胞制剂进行研究 耻垢分枝杆菌和结核分枝杆菌 H37Ra。 在现在 在该项目的阶段，正在使用化学合成来获得 戊糖D-阿拉伯糖的核苷二磷酸衍生物。 这 目的是测试这些衍生物作为 D-阿拉伯糖的主要供体 生物合成过程中的残留物。 优选合成 该过程涉及 D-阿拉伯糖糖苷化为甲基 a-D-阿拉伯呋喃糖苷，将糖苷苯甲酰化为 2,3,5-三苯甲酸酯，以及将苯甲酸酯转化为受保护的 糖基氯和/或糖基溴。 然后糖基卤化物将是 用尿苷二磷酸四丁基铵盐处理和 鸟苷二磷酸 d-阿拉伯呋喃糖。 或者， 四丁基磷酸二苄基铵可以与 受保护的阿拉伯糖基氯或溴化物，且产物脱保护 得到D-阿拉伯呋喃糖1-磷酸。 1-磷酸的反应 与核苷二磷酸的磷酸吗啉酯 兴趣应该给出相应的核苷二磷酸 阿拉伯呋喃病。 由于所有或几乎所有中间体 已描述了拟议的合成方法和两种最终产品 在文献中，可以通过检查高 获得的每种化合物的分辨率 1H NMR 谱。 为了 最终产品 13C 和 31P 光谱也可能有用。 一旦 使用普通试剂建立合成的可靠性， 将进行放射性样品的制备， 1-[14C]-D-阿拉伯糖作为标记的起始材料。