BIOLOGICALLY IMPORTANT FURANOSYL RINGS

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

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.