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.

生物学上至关重要的呋喃糖的几种特性（即溶液 构成和构象，开环和环的动力学 将研究反应（互变异）。 实验方法 涉及：A。Furanoses和Furanose结构变异的合成 所有环构型中的磷酸盐允许结构功能 比较。 化合物将用稳定的同位素（13C，2H）标记为 促进高视野NMR光谱检查。 B.识别和定量存在于互变域形式 NMR的Furanoses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）松弛 Furanosyl环中的时间（13c，1h）。 放松研究将涉及 使用沙漠和动态NOE NMR方法获得绝对1H-1H 内部距离，将评估构象。 NMR推论的首选环形构象将被比较 通过MO计算预测。 D.测量和解释单向率常数 NMR的furanose互变异。 将测量激活参数 对于每个组件反应。 简单呋喃糖的解决方案研究将扩展到 核糖核苷和寡核核苷酸。 多个GC充满 寡聚核苷酸，具有与在 大肠杆菌trnaglu的茎将准备包含 perdeutero-核呋喃糖基残基，以促进其NMR研究 解决方案结构。 拟议的研究是追求长期的先决条件 确定结合特异性的分子基础的目的 在核酸和蛋白质之间以及阐明糖的作用时 代谢调节的互变异。