SYNTHESIS OF STABLE ISOTOPE LABELED NUCLEOTIDES

15N标记的寡核苷酸，已被证明是 无价的核酸结构、药物结合和 蛋白质-核酸相互作用。在过去，我们一直专注于 单一的15N标记的嘌呤和基于嘌呤的核苷已经被 结构如下：0-2‘-脱氧-[L_15N]、[氨基-15N]、[3-15N]、 [9_15N]和[7-‘5N]腺苷；P-2’-脱氧-[L-“N]，[2_15N]，[3-15 N]和[7-“NL-鸟苷，并有足够的化学药品用量 寡核苷酸的构建。今年，我们重点研究了 乘以专门标记的核苷的15N位。这些 定点标记的核酸将导致增加 能够同时探测核酸的结构和功能 多核和多维核的生物组装 磁共振波谱实验。中讨论过的 我们开发了一种新的合成方法 [9-15N]-、[氨基-15N]或[9，氨基-15N]腺嘌呤， P-D-2‘-脱氧-[8-13C，9，氨基-15氨基-腺苷和2’-脱氧-[氨基-15 胞苷。最后，我们制定了一条通向A和G的共同路线 只有在合成结束时它才会发散。

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.