Investigations into the conformation and stability of basic nucleic acid structures and their interactions with other biologically important molecules are proposed. Knowledge of the properties of these basic structures is a key to our understanding the function of nucleic acids in the synthesis of proteins, the operation of the genetic apparatus, the regulation of cellular processes, and the mode of action of chemical agents that cause mutation and cancer. Enzymes will be used to synthesize especially interesting oligomeric components of larger nucleic acids. The purification of these oligomers will be greatly aided by a high pressure liquid chromatographic (HPLC) method we have developed. Nuclear magnetic resonance (nmr) experiments will be employed to investigate the structural details of these molecules in aqueous solution. These experiments will be correlated with studies of the absorption of ultraviolet light as the ordered nucleic acid structures are disrupted by increasing the temperature. This information bears upon the stability of the natural counterparts of these synthetic nucleic acids. Further studies on the interactions of synthetic oligonucleotides with drugs, mutagens, and metal ions will lead to inferences about the molecular basis of mutagenesis and Carcinogenesis as well as providing an approach to rational drug design.
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