BIOLOGICALLY IMPORTANT FURANOSYL RINGS

具有重要生物学意义的呋喃环

• 批准号: 3283831
• 负责人: ANTHONY STEPHEN SERIANNI
• 金额: $ 12.68万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3283831
• 关键词: anomer; carbohydrate structure; carbohydrates; chemical structure function; conformation; deuterium; enzyme mechanism; furans; isomerase; molecular orbital; monosaccharides; nuclear magnetic resonance spectroscopy; oligonucleotides; ribonucleosides; solvents; tautomer; water solution

This proposal addressed several fundamental problems in the chemistry and biochemistry of biologically-important furanose and furanose-containing compounds. The experimental approach involves the combination of stable isotopic enrichment, modern multi-pulse 1D and 2D NMR spectroscopy, and computational chemistry (ab initio molecular orbital calculations). New/improved methods (chemical and enzymic) will be developed to introduce stable isotopes (13C,2H) into carbohydrates, with particular focus on furanose sugars. By preparing systematically a variety of furanose structures, we aim to: A) Study the tautomeric composition of these (13C)-enriched furanose rings in aqueous solution as a function of ring structure/configuration. B) Study the conformational/dynamic properties of these (13C)- enriched furanoses as a function of ring structure and configuration. This will be accomplished by interpreting long- range 1H-1H, 13C-1H and 13C-13C coupling constants obtained from high-resolution NMR spectra. Theoretical input to these studies will be supplied by molecular orbital calculations (geometry optimization). C) Study how furanose ring structure/configuration, and other factors, affect the rates of ring-opening and ring-closing reactions in solution (furanose anomerization). For example, the effect of ring alkylation on these rates (Thorpe-Ingold effects) will be examined. D) Study how furanose ring conformation/dynamics are altered when incorporated into oligonucleotides; specific-sequence oligonucleotides containing stable isotopes will be used in this work. The proposed studies are a prerequisite to the pursuit of the longer-term objectives of determining the molecular basis for the binding specificity between nucleic acids and proteins, and on elucidating the effect of sugar tautomerization on metabolic regulation.

这一建议解决了《公约》中的几个基本问题。 具有重要生物学意义的呋喃糖化学和生物化学 和含呋喃糖的化合物。 实验方法 包括稳定同位素富集，现代 多脉冲1D和2D NMR光谱，以及计算 化学（从头算分子轨道计算）。 将开发新的/改进的方法（化学和酶） 将稳定同位素（13 C，2 H）引入碳水化合物中， 特别关注呋喃糖。 通过系统地准备 各种呋喃糖结构，我们的目标是： A）研究这些（13 C）富集的化合物的互变异构体组成， 水溶液中呋喃糖环作为环的函数 结构/配置。 B）研究这些（13 C）- 富集的呋喃糖作为环结构的函数， 配置. 这将通过解释长- 在1H-1H、13 C-1H和13 C-13 C范围内获得了偶合常数 从高分辨率核磁共振光谱中 理论上的投入 研究将由分子轨道计算提供 （几何优化）。 C）研究呋喃糖环结构/构型，以及其他 影响开环和闭环速率的因素 在溶液中的反应（呋喃糖端基异构化）。 比如说 环烷基化对这些速率的影响（索普-英戈尔德效应） 将被审查。 D）研究呋喃糖环构象/动力学如何改变 当掺入寡核苷酸中时;特异性序列 含有稳定同位素的寡核苷酸将用于本发明。 工作 拟议的研究是寻求 长期目标是确定 核酸和蛋白质之间的结合特异性，以及 阐明糖互变异构对代谢的影响 调控