BIOLOGICALLY IMPORTANT FURANOSYL RINGS

具有重要生物学意义的呋喃环

基本信息

批准号：
3283832
负责人：
ANTHONY STEPHEN SERIANNI
金额：
$ 13.52万
依托单位：
UNIVERSITY OF NOTRE DAME
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-12-01 至 1992-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3283832
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

项目摘要

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.

该提案解决了几个基本问题化学和生物学上最重要的呋喃糖的生物化学和含呋喃糖的化合物。实验方法涉及稳定的同位素富集，现代的结合多脉冲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）将稳定的同位素（13C，2H）引入碳水化合物中，并带有特别关注呋喃糖糖。通过系统准备各种呋喃糖结构，我们的目标是： a）研究这些（13C）富集的互变量成分水溶液中的Furanose环随环的函数结构/配置。 b）研究这些（13C） - 富集的呋喃糖作为环结构的函数，配置。这将通过解释长期来实现获得的1H-1H，13C-1H和13C-13C耦合常数来自高分辨率NMR光谱。这些的理论输入研究将通过分子轨道计算提供（几何优化）。 c）研究Furanose环的结构/配置以及其他因素，影响开环和闭环的速度溶液中的反应（Furanose呼吸症）。例如，环烷基化对这些速率的影响（Thorpe-ingold效应）将被检查。 d）研究如何改变呋喃糖环构象/动力学当掺入寡核苷酸时；具体序列在此中将使用含有稳定同位素的寡核苷酸工作。拟议的研究是追求确定分子基础的长期目标核酸和蛋白质之间的结合特异性，以及阐明糖激素化对代谢的影响规定。