Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research (ISIR), Osaka University, Mihoga-oka, Ibaraki 567-0047, Japan.
Biochemistry. 2020 Jul 28;59(29):2679-2683. doi: 10.1021/acs.biochem.0c00333. Epub 2020 Jul 9.
The methylation of cytosine in the full mutation of the expanded CGG repeat and subsequent deamination to thymine could be a measure of repeat instability. We report the synthesis of NCD-Bpy, which binds to the TGG/CGG site in the repeat hairpin. NCD-Bpy forces the thymine in the TGG/CGG site to flip out from the π-stack, recruits osmium tetroxide in the vicinity of the flipped-out T, and oxidizes the T. The piperidine-induced cleavage band successfully determined the position of the T in the expanded CGG repeat.
胞嘧啶在扩展的 CGG 重复序列中的甲基化以及随后的脱氨变为胸腺嘧啶可能是重复不稳定的一个衡量标准。我们报告了 NCD-Bpy 的合成,它与重复发夹中的 TGG/CGG 位点结合。NCD-Bpy 迫使 TGG/CGG 位点中的胸腺嘧啶从π-堆叠中翻转出来,在翻转的 T 附近招募锇四氧化物,并氧化 T。哌啶诱导的切割带成功确定了扩展的 CGG 重复中 T 的位置。