Michaelides Iacovos N, Tago Nobuhiro, Viverge Bastien, Carell Thomas
Center for Integrated Protein Science at the Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany.
Current address: AstraZeneca, 310 Cambridge Science Park, Milton Road, Cambridge, CB4 0FZ, UK.
Chemistry. 2017 Nov 13;23(63):15894-15898. doi: 10.1002/chem.201704216. Epub 2017 Oct 20.
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.
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中发现的新型表观遗传碱基（hmdC、fdC、cadC）。相同的碱基（5-羟甲基胞苷、5-甲酰基胞苷和5-羧基胞苷；hmC、fC和caC）现在也已在哺乳动物RNA中检测到，在mRNA中含量很高。虽然已有用于合成含xdC的寡核苷酸以进行更深入生物学研究的DNA亚磷酰胺（PAs），但尚未公开用于fC和caC的相应硅烷基保护的RNA PAs。在此，我们报告了可用于常规RNA合成的新型用于hmC、fC和caC的RNA PAs。这些新的构建模块与标准PAs兼容，彼此之间也兼容，这使得甚至能够合成包含所有这三种碱基的RNA链。该研究将为详细的物理、生化和生物学研究铺平道路，以揭示这些RNA中非经典修饰的功能。
