METAL MEDIATED MOLECULAR AGGREGATES OF GUANINE AND ADENINE NUCLEOTIDES

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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.