Organic and Biomimetic Chemistry Research Group, Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Gent (Belgium).
Chembiochem. 2014 Jan 3;15(1):103-7. doi: 10.1002/cbic.201300612. Epub 2013 Dec 9.
We have previously developed a crosslinking methodology for oligonucleotides based on the incorporation of furan moieties, which can be selectively oxidised to reactive intermediates that will quickly react with the opposite bases in DNA, forming toxic interstrand crosslinks (ICLs). Furan moieties also occur in natural DNA, as a result of oxidative stress. Moreover, the furan-containing degradation product of this modified DNA-kinetin-has been found to display beneficial anti-ageing effects. To investigate the apparent discrepancy between the effects of the synthetic and the natural furan modifications in DNA, a quick and easy postsynthetic method providing access to the natural modification in short synthetic oligonucleotides was developed. On checking for potential crosslinking propensity, we found that the furan moiety does indeed undergo oxidation, in this way functioning as an important scavenger for oxidative stress. The reactive intermediate, however, was shown to degrade without producing toxic crosslinked products.
我们之前开发了一种基于呋喃部分的寡核苷酸交联方法，呋喃部分可以选择性地氧化为反应性中间体，这些中间体将迅速与 DNA 中的相反碱基反应，形成有毒的链间交联（ICLs）。呋喃部分也存在于天然 DNA 中，是氧化应激的结果。此外，已发现这种修饰的 DNA-激动素的含呋喃的降解产物具有有益的抗衰老作用。为了研究合成和天然呋喃修饰在 DNA 中作用的明显差异，开发了一种快速简便的后期合成方法，可在短合成寡核苷酸中获得天然修饰。在检查潜在的交联倾向时，我们发现呋喃部分确实会发生氧化，因此作为氧化应激的重要清除剂。然而，反应性中间体被证明没有产生有毒的交联产物就降解了。
