SYNTHESIS OF STABLE ISOTOPE LABELED NUCLEOTIDES

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15 N Labeled oligonucleotides, have been demonstrated to be invaluable probes of nucleic acid structure, drug-binding, and protein-nucleic acid interactions. In the past we have focused on the single 15N labeled purines and purine based nucleosides have been constructed such as, 0-2'-deoxy-[l_ 15 N], [amino- 15 N], [3- 15 N], [9_ 15 N] and [7-'5N]adenosines; P-2'-deoxy-[l-"N], [2_15 N], [3- 15 N], and [7-"Nl-guanosines and in sufficient quantity for chemical construction of oligonucleotides. This year we focused syntheses of multiply 15 N site specifically labeled nucleosides. These site-specifically labeled nucleic acids will give rise to increased ability to probe both the structure and function of nucleic acid biological assemblies by multinuclear and multidimensional nuclear magnetic resonance spectroscopy experiments. As discussed in the progress report we have developed new method for the synthesis of [9-15 N]-, [amino- 15 N] or [9,amino- 15 N2]adenine, P-D-2'-deoxy-[8-13C, 9,amino- 15 Njadenosine, and 2'-deoxy-[amino- 15 N]cytidine. Finally, we have developed a common route to A and G that it only diverges at the end of the synthesis.