Institute of Organic Chemistry, Faculty of Chemistry, University of Technology, 90-924 Lodz, Zeromskiego 116, Poland.
Org Biomol Chem. 2024 Sep 18;22(36):7271-7286. doi: 10.1039/d4ob01098a.
Studies of 5-hydroxymethylcytidine (hmC), 5-formylcytidine (fC) and 5-carboxycytidine (caC) modifications as products of the 5-methylcytidine (mC) oxidative demethylation pathway in cellular mRNAs constitute an important element of the new epitranscriptomic field of research. The dynamic process of mC conversion and final turnover to the parent cytidine is considered a post-transcriptional layer of gene-expression regulation. However, the regulatory mechanism associated with epitranscriptomic cytidine modifications remains largely unknown. Therefore, oligonucleotides containing mC oxidation products are of great value for the next generation of biochemical, biophysical, and structural studies on their function, metabolism, and contribution to human diseases. Herein, we summarize the synthetic strategies developed for the incorporation of hmC, fC and caC into RNA oligomers by phosphoramidite chemistry, including post-synthetic C5-cytidine functionalization and enzymatic methods.
研究 5-羟甲基胞嘧啶（hmC）、5-甲酰胞嘧啶（fC）和 5-羧基胞嘧啶（caC）修饰作为细胞 mRNA 中 5-甲基胞嘧啶（mC）氧化去甲基化途径产物，构成了新的表观转录组学研究领域的重要组成部分。mC 转换的动态过程以及最终转化为母核嘧啶的过程被认为是基因表达调控的转录后层。然而，与表观转录组学胞嘧啶修饰相关的调节机制在很大程度上仍是未知的。因此，含有 mC 氧化产物的寡核苷酸对于下一代关于其功能、代谢以及对人类疾病贡献的生化、生物物理和结构研究具有重要价值。在此，我们总结了通过亚磷酰胺化学将 hmC、fC 和 caC 掺入 RNA 寡聚物的合成策略，包括 C5-胞嘧啶的后合成功能化和酶法。
