The objectives of this proposal are to determine the crystal and molecular structures of selected nucleic acid constituents with the view of understanding their biological properties, interactions and functions. Structural studies are underway on: (a) metal-nucleotide and metal-polyphosphate complexes, (b) modified nucleosides and nucleotides including alkylated nucleotides, (c) deoxyoligonucleotides and DNA fragments and (d) drug- and dye-nucleotide complexes. Studies are underway on metal complexes containing mixed ammine and aquo ligands, sulphur substitution in the phosphate and also to metal ions such as rhodium in addition to Cr3+, Zn2+, Mn2+, Co2+, Ca2+ and Mg2+. The metal-nucleotide and metal-polyphosphate studies are being done in collaboration with Dr. Dunaway-Mariano (Univ. of Maryland), Dr. Richard Cornelius (Univ. of Wichita), Dr. W. Wallace Cleland (Univ. of Wisconsin), and Dr. Renzo Cini (Univ. of Florence). X-ray structures and NMR investigations of modified nucleosides and base O-alkylated nucleosides are being carried out in collaboration with Dr. Frank Hruska (Univ. of Manitoba) and phosphate O-alkylated nucleotides in collaboration with Dr. Norman Kondo (Univ. District of Columbia, Washington, DC). Studies are underway on the following deoxyoligonucleotides (ii) CGTACGTACG, (iii) CGTATATACG and (iii) CGCGCCCCGCG. (i) and (ii) have already been crystallized. We are also setting up facilities for DNA oligomer synthesis. The above structural studies will provide information on variability in nucleic acid structures, and principles controlling coordination of nucleotides which aid our understanding of the use of metal-substrates as probes in enzyme specificity and mechanism. The work on oligonucleotides will provide useful information on sequence-dependent conformational variations in DNA structure which is important in understanding gene expression and regulation.
