MOLECULAR AND SUPRAMOLECULAR AGGREGATES IN GUANINE AND ADENINE NUCLEOTIDES

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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.