Convenient synthesis of pyrimidine 2'-deoxyribonucleoside monophosphates with important epigenetic marks at the 5-position.,Organic & Biomolecular Chemistry

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Convenient synthesis of pyrimidine 2'-deoxyribonucleoside monophosphates with important epigenetic marks at the 5-position.
Organic & Biomolecular Chemistry ( IF 2.9 ) Pub Date : 2020-06-23 , DOI: 10.1039/d0ob00884b
Song Zheng ₁ , Ai Tran ₁ , Alyson M Curry ₂ , Dawanna S White ₂ , Yana Cen ₃

Affiliation

Methyl groups of thymine and 5-methylcytosine (5^mC) bases in DNA undergo endogenous oxidation damage. Additionally, 5^mC residues can be enzymatically deaminated or oxidized through either genetic alterations or the newly identified epigenetic reprogramming pathway. Several methods have been developed to measure the formation of modified DNA nucleobases including ³²P-postlabeling. However, the postlabeling method is often limited by the absence of authentic chemical standards. The synthesis of monophosphate standards of nucleotide oxidation products is complicated by the presence of additional functional groups on the modified bases that require complex protection and deprotection strategies. Due to the emerging interest in the pyrimidine oxidation products, the corresponding protected 3′-phosphoramidites needed for solid-phase oligonucleotide synthesis have been reported, and several are commercially available. We report here an efficient synthesis of 3′-monophosphates from 3′-phosphoramidites and the subsequent enzymatic conversion of 3′-monophosphates to the corresponding 5′-monophosphates using commercially available enzymes.

中文翻译：

方便合成嘧啶 2'-脱氧核糖核苷单磷酸，在 5 位具有重要的表观遗传标记。

DNA中胸腺嘧啶的甲基和 5-甲基胞嘧啶 (5 ^m C) 碱基会受到内源性氧化损伤。此外，5 ^m C 残基可以通过基因改变或新发现的表观遗传重编程途径进行酶促脱氨基或氧化。已经开发了几种方法来测量修饰的 DNA 核碱基的形成，包括³²P-后标记。然而，后标记方法通常受到缺乏真实化学标准的限制。由于修饰碱基上存在额外的官能团，需要复杂的保护和脱保护策略，因此核苷酸氧化产物的单磷酸标准的合成变得复杂。由于对嘧啶氧化产物的兴趣日益浓厚，已经报道了固相寡核苷酸合成所需的相应受保护的 3'-亚磷酰胺，并且有几种是可商购的。我们在此报告了从 3'-亚磷酰胺有效合成 3'-单磷酸酯以及随后使用市售酶将 3'-单磷酸酯酶促转化为相应的 5'-单磷酸酯。

更新日期：2020-07-15

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