15N-multilabeled adenine and guanine nucleosides.: Syntheses of [1,3,NH2-15N3]- and [2-13C-1,3,NH2-15N3]-labeled adenosine, guanosine, 2′-deoxyadenosine, and 2′-deoxyguanosine
15N-multilabeled adenine and guanine nucleosides.: Syntheses of [1,3,NH2-15N3]- and [2-13C-1,3,NH2-15N3]-labeled adenosine, guanosine, 2′-deoxyadenosine, and 2′-deoxyguanosine
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DOI：
10.1021/jo982372k
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发表时间：
1999-09-03
影响因子：
3.6
通讯作者：
Jones, RA
中科院分区：
文献类型：
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作者：
Abad, JL;Gaffney, BL;Jones, RA
我们报道了一种高产率的路线，得到以下特异性N-15-和C-1,3-多标记核苷：[1，3，NH 2-N-15（3）]-和[2-C-1,3 -1，3，NH 2-N-15（3）]-腺苷; [1，3，NH 2-N-15（3）]-和[2-C-1,3 - 1，3，-NH 2-N-15（3）]-2 '-脱氧鸟苷。[1，3，NH 2-N-15（3）]-和[2-C-1,3 -1，3，NH 2-N-15（3）]-2 '-脱氧腺苷; [1，3，NH 2-N-15（3）]-和[2-C-1,3 - 1，3，-NH 2-N-15（3）]-2'-脱氧鸟苷。在每一组中，（13）C2原子作为一个“标签”，允许（15）N1和（15）N3原子明确区分RNA或DNA片段的N-15 NMR中未标记的版本。腺嘌呤核苷和鸟嘌呤核苷合成策略的关键中间体是[NH 2，CONH 2-N-15（2）]-5-氨基-4-咪唑甲酰胺。使用[C-13]-乙基黄原酸钠（（NaSCSOEt）-C-13）通过闭环添加[2-C-13]-标记。多标记的6-氯嘌呤或多标记的2-巯基次黄嘌呤的酶促转糖基化和与（NH3）-N-15的最终反应得到腺嘌呤和鸟嘌呤核苷。这是首次报道[3-N-15]-标记鸟嘌呤核苷。
We report a high-yield route to the following specifically N-15- and C-13-multilabeled nucleosides:[1,3,NH2-N-15(3)]- and [2-C-13-1,3,NH2-N-15(3)]-adenosine; [1,3,NH2-N-15(3)]- and [2-C-13-1,3,-NH2-N-15(3)]-2'-deoxyguanosine. [1,3,NH2-N-15(3)]- and [2-C-13-1,3,NH2-N-15(3)]-2'-deoxyadenosine; [1,3,NH2-N-15(3)]- and [2-C-13-1,3,-NH2-N-15(3)]-2'-deoxyguanosine. In each set, the (13)C2 atom functions as a "tag" that allows the (15)N1 and (15)N3 atoms to be unambiguously differentiated from the untagged versions in N-15 NMR of RNA or DNA fragments. The key intermediate of this synthetic strategy for both the adenine and guanine nucleosides is [NH2, CONH2-N-15(2)]-5-amino-4-imidazolecarboxamide. The [2-C-13]-label is added through a ring closure using [C-13]-sodium ethyl xanthate ((NaSCSOEt)-C-13). Enzymatic transglycosylation of either multilabeled 6-chloropurine or multilabeled 2-mercaptohypoxanthine and a final reaction with (NH3)-N-15 give the adenine and guanine nucleosides. This is the first report of a [3-N-15]-labeled guanine nucleoside.