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结合成G-四聚体(一种氢键碱基的环状四聚体)，G-四聚体具有形成四链螺旋结构的能力。这些结构已经在模拟位于染色体末端的端粒的序列中被识别出来，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，并为此类生物分子系统的功能提供见解。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-四元结构相匹配或显著改变结构，作为这一研究的一部分，将检查导致Friedreich‘s共济失调的三重重复GAA，并将确定可能在这种疾病中发挥作用的自相关结构；(2)继续测定GPG和d(GPG)聚集体的大小、分子结构和构象；(3)不同碱金属离子，特别是钠、钾离子和碱土、镁离子对上述核苷酸结构影响的研究：(4)重金属锡对四元和超分子核苷酸结构影响的初步研究。三丁基锡化合物是常用的杀生剂，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，还将在极性有机溶剂中研究一些核苷酸。使用的技术包括核磁共振、红外和紫外光谱、凝胶电泳法和分析性超速离心法。

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.