Bioactivatable reductive cleavage of azobenzene for controlling functional dumbbell oligodeoxynucleotides

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.