The long term objectives of this research are as follows: (1) Develop a chemical methodology for synthesizing RNA and branched RNA. Our preliminary experiments suggest that this objective can best be achieved by focusing on the use of a silica based polymer support and a 3' to 5' synthesis methodology utilizing nucleoside phosphoramidites as synthons. Specific problems which must be addressed include the 2', phosphorus and base protecting groups as well as the method of attachment of the growing RNA segment to the support. (2) Develop a genetic assay for screening DNA chemical synthesis methodologies and use this assay to improve current procedures for DNA synthesis. Many problems in DNA synthesis methodologies that lead to genetic mutations cannot easily be monitored using current analytical or purification procedures. This problem can best be solved by developing a genetic screen for surveying various chemical procedures. The establishment of this assay as outlined in this grant application when coupled with its use to monitor proposed improvements in methodologies should lead to a superior DNA synthesis approach. (3) Develop new analogs useful for studying proteinDNA interactions in gene control regions. These analogs would be found within deoxyoligonucleotides at specific, predefined positions and would be selected for synthesis based upon how they might alter protein DNA interaction sites.
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