SYNTHESIS OF STABLE ISOTOPE LABELED NUCLEOTIDES

15 N标记的寡核苷酸，已被证明是 核酸结构、药物结合和 蛋白质-核酸相互作用 在过去，我们一直专注于 单个15 N标记的嘌呤和基于嘌呤的核苷已经被 例如，0- 2 ′-脱氧-[1 - 15 N]，[氨基-15 N]，[3- 15 N]， [9 - 15 N]和[7 - 15 N]腺苷; P-2 '-脱氧-[1-“N]，[2 - 15 N]，[3- 15 N]和[7-Nl-鸟苷，以及足够量的化学制剂。 寡核苷酸的构建。 今年，我们将重点放在 多个15 N位点特异性标记的核苷。 这些 位点特异性标记的核酸将增加 探测核酸结构和功能的能力 多核和多维核生物组装 磁共振波谱实验 中所讨论 进展报告我们已经开发了新的方法合成 [9-15 N]-、[氨基-15 N]或[9，氨基-15 N2]腺嘌呤， β-D-2 ′-脱氧-[8- 13 C，9，氨基-15 N]腺苷和2 ′-脱氧-[氨基-15 N]胞苷。 最后，我们开发了一条通往A和G的通用路线， 它只在合成结束时发散。

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.