METAL MEDIATED MOLECULAR AGGREGATES OF GUANINE AND ADENINE NUCLEOTIDES

含有几个连续鸟嘌呤残基的核苷酸经常自缔合成G-四聚体（氢键碱基的环状四聚体），其具有形成四链螺旋结构的能力。这些结构已经在模拟染色体末端端粒的序列中被鉴定出来，并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有关核苷酸在溶液中如何行为的具体详细信息，这将允许描绘大分子结构，并提供对此类生物分子系统功能的见解。具体目标包括：（1）鸟嘌呤-腺嘌呤二-和寡核苷酸的研究，其目的是阐明腺嘌呤残基如何与G-四联体结构配合或显著改变结构，作为其一部分，将检查导致弗里德赖希共济失调的三联体重复GAA，并将确定可能在这种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（特别是钠和钾）和碱土金属离子（镁）引起的上述核苷酸结构的差异;（4）初步探讨了重金属锡对四联体和超分子核苷酸结构的影响。三丁基锡化合物是广泛使用的生物杀灭剂，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之外，一些核苷酸将在极性有机溶剂中进行研究。使用的技术包括NMR、IR和紫外光谱、凝胶电泳和分析超离心。

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.