Synthesis of RNA Containing 5-Hydroxymethyl-, 5-Formyl-, and 5-Carboxycytidine.
Synthesis of RNA Containing 5-Hydroxymethyl-, 5-Formyl-, and 5-Carboxycytidine.
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DOI：
10.1002/chem.201704216
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发表时间：
2017-11
期刊：
影响因子：
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通讯作者：
Iacovos N Michaelides;Nobuhiro Tago;Bastien Viverge;T. Carell
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文献类型：
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作者：
Iacovos N Michaelides;Nobuhiro Tago;Bastien Viverge;T. Carell
5-羟甲基、5-甲酰基和5-羧基-2‘-脱氧胞苷是最近在高等真核生物DNA中发现的新的表观遗传碱基(hmdC、FDC、CADC)。同样的碱基(5-羟甲基、5-甲酰基和5-羧基胞苷；HMC、FC和CAC)现在也在高丰度的mRNA的哺乳动物RNA中被检测到。虽然可以合成用于更深入生物学研究的含XDC的寡核苷酸的DNA磷酰胺(PAS)，但对应的用于FC和CAC的硅基保护的RNA PAS尚未被披露。在这里，我们报告了可用于常规RNA合成的针对HMC、FC和CAC的新型RNA PAS。新的构建单元与规范的PA兼容，也与它们自身兼容，这使得甚至可以合成包含所有这三个碱基的RNA链。这项研究将为详细的物理、生化和生物学研究铺平道路，以揭示RNA中这些非规范修饰的功能。
5-Hydroxymethyl-, 5-formyl-, and 5-carboxy-2'-deoxycytidine are new epigenetic bases (hmdC, fdC, cadC) that were recently discovered in the DNA of higher eukaryotes. The same bases (5-hydroxymethyl-, 5-formyl-, and 5-carboxycytidine; hmC, fC, and caC) have now also been detected in mammalian RNA with a high abundance in mRNA. While DNA phosphoramidites (PAs) that allow the synthesis of xdC-containing oligonucleotides for deeper biological studies are available, the corresponding silyl-protected RNA PAs for fC and caC have not yet been disclosed. Here, we report novel RNA PAs for hmC, fC, and caC that can be used in routine RNA synthesis. The new building blocks are compatible with the canonical PAs and also with themselves, which enables even the synthesis of RNA strands containing all three of these bases. The study will pave the way for detailed physical, biochemical, and biological studies to unravel the function of these non-canonical modifications in RNA.