Department School of Pharmacy Institution, Jiangxi Science & Technology Normal University, Jiangxi 330013, China.
School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 101408, China.
Bioorg Chem. 2019 Oct;91:103106. doi: 10.1016/j.bioorg.2019.103106. Epub 2019 Jul 3.
Application of stimuli-responsive bioactive molecules is an attractive strategy due to use for target special tissues and cells. Here, we reported synthesis of an azo-linker, 2,2'-dimethoxyl-4,4'-dihydroxymethylazobenzene (mAzo), which was more effectively recognized and cleaved by reducing glutathione (GSH) via comparing with 4,4'-dihydroxymethylazobenzene (Azo). In addition, mAzo is further exploited to engineer dumbbell asODNs, which could result in the release of asODNs and thus modulate their hybridization to target nucleic acids. The present study is the first example to disclose efficient reductive cleavage of azobenzene by GSH to generate aromatic amine. This would provide a valuable strategy for tunable cell-specific release of ODNs and modulation of known disease-causing gene expression in cancer cells.
由于刺激响应生物活性分子可用于靶向特殊组织和细胞，因此其应用具有吸引力。在这里，我们报告了一种偶氮键联物，2,2'-二甲氧基-4,4'-二羟甲基偶氮苯（mAzo）的合成，与 4,4'-二羟甲基偶氮苯（Azo）相比，它通过还原型谷胱甘肽（GSH）更有效地被识别和切割。此外，mAzo 进一步被用于构建哑铃状 asODNs，这可以导致 asODNs 的释放，从而调节其与靶核酸的杂交。本研究首次揭示了 GSH 对偶氮苯的有效还原裂解以生成芳香胺。这将为 ODNs 的可调节细胞特异性释放和调节癌细胞中已知致病基因的表达提供有价值的策略。
