BIOLOGICALLY IMPORTANT FURANOSYL RINGS

这项建议解决了 具有重要生物意义的呋喃糖的化学和生物化学 以及含呋喃糖类化合物。实验方法 涉及稳定同位素浓缩的组合，现代 多脉冲一维和二维核磁共振波谱，并计算 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) 将稳定的同位素(13C，2H)引入碳水化合物， 特别关注呋喃糖类。通过系统地准备 各种呋喃糖结构，我们的目标是： A)研究这些富含(13C)的互变异构体的组成 水溶液中呋喃糖环与环的函数关系 结构/配置。 B)研究这些(13C)-的构象/动力学性质 作为环结构函数的富含呋喃类化合物 配置。这将通过解释Long- 获得了1H-1H、13C-1H和13C-13C耦合常数范围 来自高分辨率的核磁共振波谱。对这些的理论投入 研究将由分子轨道计算提供。 (几何体优化)。 C)研究呋喃糖环结构/构型，以及其他 影响开环率和合环率的因素 溶液反应(呋喃糖异构化)。例如， 环烷基化对这些速率的影响(索普-金氏效应) 将会被检查。 D)研究呋喃糖环的构象/动力学如何改变 当被掺入寡核苷酸时；特定序列 含有稳定同位素的寡核苷酸将用于这一领域 工作。 建议的研究是进行 确定分子基础的较长期目标 核酸和蛋白质之间的结合特异性，以及 阐明糖的互变异构化对代谢的影响 监管。

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.