The purpose of this research is to produce stable isotopically labeled reagents for synthesis of uniformly labeled nucleic acids. These will be useful as a tool in the determination of nucleic acid structure as well as elucidation of their interaction with other biological macromolecules. This is an expansion of the Phase I research goals. During Phase I, we concentrated on production of both unlabeled and deuterated ribonucleosides. That initial work allows us to confidently go forward with a broader project that includes production of blocked ribo- and deoxyribonucleotides for use as reagents for oligonucleotide synthesis, and custom synthesis of uniformly labeled oligonucleotides. We will complete the RNA project: 1) completing the work begun during Phase I (i.e. the production of ribonucleosides), 2) producing protected ribonucleotides, and 3) synthesizing uniformly labeled oligonucleotides. Once the process has been completed for RNA, the same scope of research will be carried out on deoxyribonucleosides and their blocked derivatives. A successful completion of this project will provide a cost effective means for production of each of the four major ribonucleosides (protected and naked), the four major deoxyribonucleosides (protected and naked), two mixtures containing either deoxyribo- or ribonucleotides, and a system (or systems) for production of custom made DNA's or RNA's containing uniformly stable isotopically labeled oligonucleotides or uniformly labeled individual bases in specific positions as required for the individual research project.
