BIOLOGICALLY-IMPORTANT FURANOSYL RINGS

具有重要生物学意义的呋喃环

• 批准号: 3283830
• 负责人: ANTHONY STEPHEN SERIANNI
• 金额: $ 7.88万
• 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 1988-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3283830
• 关键词: Escherichia coli; acidity /alkalinity; chemical structure function; conformation; furans; high performance liquid chromatography; molecular orbital; nonradiation isotope effect; nuclear magnetic resonance spectroscopy; oligonucleotides; ribonucleosides; solvents; tautomer; temperature; thermodynamics; transfer RNA; water solution

Several properties of biologically-important furanoses (i.e., solution composition and conformation, and kinetics of ring-opening and ring-closing reactions (tautomerization) will be studied. The experimental approach involves: A. Synthesis of structural variants of furanoses and furanose phosphates in all ring configurations to permit structure-function comparisons. Compounds will be labeled with stable isotopes (13C, 2H) to facilitate examination by high-field NMR spectroscopy. B. Identification and quantitation of the tautomeric forms present in aqueous solutions of furanoses by NMR, with particular attention given to carbonyl and hydrate forms. C. Measurement and conformational interpretation of three-bond 1H-1H, 13C-1H and 13C-13C coupling constants and spin-lattice (T1) relaxation times (13C, 1H) in furanosyl rings. Relaxation studies will involve the use of DESERT and dynamic NOE NMR methods to obtain absolute 1H-1H internuclear distances, from which conformation will be assessed. Preferred ring conformations deduced by NMR will be compared to those predicted by MO calculations. D. Measurement and interpretation of unidirectional rate constants of furanose tautomerization by NMR. Activation parameters will be measured for each component reaction. Solution studies of simple furanoses will be extended to the ribonucleosides and oligoribonucleotides. Several GC-rich oligoribonucleotides, having base sequences identical to those found in the stems of E. coli tRNAglu, will be prepared containing perdeutero-ribofuranosyl residues to facilitate NMR studies of their solution structures. The proposed studies are a prerequisite to the pursuit of the longer-term objective 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.

具有重要生物学意义的呋喃糖的几个特性（即溶液 组成和构象，以及开环和闭环动力学 将研究反应（互变异构）。 实验方法 涉及： A. 呋喃糖和呋喃糖结构变体的合成 所有环构型中的磷酸盐以允许结构功能 比较。 化合物将用稳定同位素 (13C, 2H) 标记 便于通过高场核磁共振波谱进行检查。 B. 互变异构形式的鉴定和定量 通过 NMR 测定呋喃糖水溶液，特别注意 羰基和水合物形式。 C. 三键 1H-1H 的测量和构象解释， 13C-1H 和 13C-13C 耦合常数和自旋晶格 (T1) 弛豫 呋喃糖基环中的次（13C，1H）。 松弛研究将涉及 使用DESERT和动态NOE NMR方法获得绝对1H-1H 核间距离，从中评估构象。 通过 NMR 推导的优选环构象将与那些 通过 MO 计算预测。 D.单向速率常数的测量和解释 通过 NMR 进行呋喃糖互变异构化。 将测量激活参数 对于每个组分反应。 简单呋喃糖的溶液研究将扩展到 核糖核苷和寡核糖核苷酸。 几种富含GC的 寡核糖核苷酸，其碱基序列与在 大肠杆菌 tRNAglu 的茎，将被制备为含有 全氘代呋喃核糖基残基以促进其核磁共振研究 解决方案结构。 拟议的研究是追求长期目标的先决条件 确定结合特异性的分子基础的目的 核酸和蛋白质之间的关系，以及阐明糖的影响 互变异构对代谢调节的影响。