Lartia Rémy, Constant Jean-François
J Org Chem. 2015 Jan 16;80(2):705-10. doi: 10.1021/jo502170e.
Hydrogen atom abstraction from the C5′-position of nucleotides in DNA results in direct strand scission by generating alkali-labile fragments from the oxidized nucleotide. The major damage consists in a terminus containing a 5′-aldehyde as part of an otherwise undamaged nucleotide. Moreover it is considered as a polymorphic DNA strand break lesion since it can be borne by any of the four nucleosides encountered in DNA. Here we propose an expeditious synthesis of oligonucleotides (ON) ending with this 5′-aldehyde group (5′-AODN). This straightforward and cheap strategy relies on Pfitzner–Moffatt oxidation performed on solid support followed by a transient protection of the resulting aldehyde function. This method is irrespective of the 5′-terminal nucleobase and most interestingly can be directly extended to RNA to produce the corresponding 5′-AORN. We also report preliminary results on recognition of 5′-AODN by base excision repair (BER) enzymes.
从DNA中核苷酸的C5′位提取氢原子会通过从氧化的核苷酸生成碱不稳定片段而导致直接链断裂。主要损伤在于一个末端含有5′-醛基，该醛基作为未受损核苷酸的一部分。此外，它被认为是一种多态性DNA链断裂损伤，因为它可以由DNA中遇到的四种核苷中的任何一种携带。在此，我们提出了一种快速合成以这种5′-醛基结尾的寡核苷酸（ON）（5′-AODN）的方法。这种直接且廉价的策略依赖于在固体支持物上进行的Pfitzner-Moffatt氧化，随后对生成的醛基功能进行短暂保护。该方法与5′-末端核碱基无关，最有趣的是可以直接扩展到RNA以产生相应的5′-AORN。我们还报告了碱基切除修复（BER）酶对5′-AODN识别的初步结果。
