METAL MEDIATED MOLECULAR AGGREGATES OF GUANINE AND ADENINE NUCLEOTIDES

含有几个相邻鸟嘌呤残基的核苷酸经常自结合成g -四聚体（氢键碱基的环状四聚体），具有形成四链螺旋结构的能力。这些结构已经在序列中被确定，这些序列模拟了染色体末端的端粒，并为它们提出了一系列生物学功能。这项研究的一个广泛目标是提供关于核苷酸在溶液中如何行为的具体、详细的信息，这将允许描绘大分子结构，并提供对这种生物分子系统功能的见解。具体目标包括：(1)研究鸟嘌呤-腺嘌呤二核苷酸和寡核苷酸，目的是阐明腺嘌呤残基如何与g -四体结构相适应或显著改变结构，作为该研究的一部分，将检查导致弗里德赖希共济失调的三重重复GAA，并确定可能在该疾病中起作用的自相关结构；(2)继续测定GpG和d（GpG）聚集体的大小、分子结构和构象；(3)研究不同碱金属离子（特别是钠、钾）和碱土（镁）对上述核苷酸的诱导结构差异；(4)初步研究重金属锡对四聚体和超分子核苷酸结构的影响。三丁基锡化合物被广泛用作一般杀菌剂，一些二取代有机锡化合物已显示出抗肿瘤活性。除了在水溶液中的实验外，一些核苷酸将在极性有机溶剂中进行研究。将使用的技术包括核磁共振、红外和紫外光谱、凝胶电泳和分析性超离心。

Nucleotides which contain several contiguous guanine residues frequently self-associate into G-tetrads (a cyclic tetramer of hydrogen-bonded bases) which have the ability to form four-stranded helical structures. These structures have been identified in sequences which model the telomeres found at the ends of chromosomes and a range of biological functions have been proposed for them. A broad goal of this research is to provide the specific, detailed information about how nucleotide behavior in solution which will allow delineation of the macromolecular structures and provide insights into the function of such biomolecular systems. Specific objectives include: (1) a study of guanine-adenine di- and oligonucleotides with the objective of elucidating how the adenine residues fit with the G-tetrad structure or dramatically change the structure, as part of this, the triplet repeat GAA, which causes Friedreich's ataxia, will be examined and the self-associated structures which may play a role in this disease will be determined; (2) a continuation of the determination of the size and molecular structure and conformation of GpG and d(GpG) aggregates; (3) a study of the differences in the structure induced by the different alkali metal ions, particularly sodium and potassium, and the alkaline earth, magnesium, for the above nucleotides; (4) an initial investigation of the effect of the heavy metal, tin, on the tetrad and supramolecular nucleotide structures. Tributyltin compounds are extensively used as general biocides and some disubstituted organotin compounds have shown anti-tumor activity. In addition to experiments in aqueous solution, some nucleotides will be investigate in polar organic solvents. The techniques to be used include NMR, IR, and ultraviolet spectroscopy, gel electrophoresis, and analytical ultracentrifugation.