MOLECULAR AND SUPRAMOLECULAR AGGREGATES IN GUANINE AND ADENINE NUCLEOTIDES

鸟嘌呤和腺嘌呤核苷酸中的分子和超分子聚集体

• 批准号: 6240208
• 负责人: JUDITH A WALMSLEY
• 金额: $ 10.6万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6240208
• 关键词: adenine nucleotides; analytical ultracentrifugation; cations; chemical bond; dinucleotide; gel electrophoresis; guanine nucleotides; high performance liquid chromatography; hydrogen bond; intermolecular interaction; lithium; metal complex; nuclear magnetic resonance spectroscopy; potassium; rubidium; sodium; spermidine; stereochemistry; ultraviolet spectrometry; water solution

In aqueous solution, the guanine nucleotides form aggregates of various sizes, depending upon the nature of the counterion, the nucleotide concentration, pH, and temperature. G-tetrad structures, which are formed with certain G-oligonucleotides, have been postulated to the biologically important in such processes as telomere replication, meiosis, homodimerization of RNA in the HIV-1 virus, and in the inhibition of macrophage scavenger receptors. The proposed research is composed of several inter-related and overlapping sections. (1) The nature of the guanine mono- and dinucleotide species (small, intermediate-sized, and very large) formed ina the presence of tetramethylammonium, Li+, Na+, K+ will continue to be elucidated. The hydrogen-bonding scheme(s), and some cases the metal ion binding site, in the small and intermediate-sized aggregates will be investigated with NMR, particularly 1H in H2), 13C, 15N, and 6Li. The supramolecular aggregates and the cation effects on their formation will be investigated by gel electrophoresis and analytical ultracentrifugation ot obtain information about their size,and molecular mass. (2) Alkali metal ion interaction with the nucleobase has been thought to stabilize the G-tetrad structure for a long time, but different experimental techniques have given conflicting data. A new hypothesis is proposed here in which the alkali metal ion (Na orK) is interacting with the pi electron system of the nucleobase. This will be tested by studying the interactions of alkali metal salts with guanine and adenine bases and nucleosides. (3) Studies similar to those on the guanine mono- and dinucleotides will be extended to adenine mono- and dinucleotides, including ApA, GpA, ApG, and their 2'-deoxy analogs. These nucleotide have the potential to form tetrad structures. The interactions of alkali metal ions with adenine residues is important to bending in double helical DNA. (4) Hydrogen bonding (without base stacking) and the reverse micellar behavior of 5'-GMP in polar organic solvents will be investigated. These systems may have application in the transport of drugs through cell membranes.

在水溶液中，鸟嘌呤核苷酸形成各种聚合物。 大小，取决于计数器的性质，核苷酸 浓度、pH和温度。 G-四分体结构， 与某些G-寡核苷酸，已被假定为生物学 在端粒复制，减数分裂， HIV-1病毒中RNA的同源二聚化，以及 巨噬细胞清道夫受体 拟议的研究包括 几个相互关联和重叠的部分。 (1)的性质 鸟嘌呤单和二核苷酸种类（小的、中等大小的和非常小的） 大）在四甲基铵的存在下形成，Li+、Na+、K+将 继续被阐明。 氢键方案，以及一些情况 金属离子结合位点，在小型和中型聚集体中 将用NMR研究，特别是H2中的1H）、13 C、15 N和6Li。 超分子聚集体及其阳离子效应 将通过凝胶电泳和分析 超离心以获得关于它们的大小和分子量的信息， 马萨诸塞州 (2)碱金属离子与核碱基的相互作用已经被证实。 被认为可以长时间稳定G-四分体结构，但不同的是， 实验技术给出了相互矛盾的数据。 一个新的假设是， 这里提出的碱金属离子（Na或K）与 核碱基的π电子系统。 这将通过研究 碱金属盐与鸟嘌呤和腺嘌呤碱基的相互作用， 核苷 (3)与鸟嘌呤单核苷酸和单核苷酸类似的研究 二核苷酸将延伸到腺嘌呤单核苷酸和二核苷酸， 包括阿帕、GpA、ApG和它们的2 ′-脱氧类似物。 这些核苷酸具有 形成四分体结构的可能性。 碱金属的相互作用 含腺嘌呤残基的离子对双螺旋DNA的弯曲是重要的。 (4)氢键（无碱基堆积）和反胶束 将研究5 '-GMP在极性有机溶剂中的行为。 这些 系统可应用于药物通过细胞的运输 膜。