New quinoline-based caging groups synthesized for photo-regulation of aptamer activity

A series of quinoline-based photo-removable protecting groups for photo-regulation of thrombin aptamer (HD1) activity were synthesized with improved caging and uncaging efficiency. Among them, 8-bromo-2-diazomethyl-7-hydroxyquinolinyl (BHQ-diazo, 1) chromophore was found to cage the HD1 with highest caging and restoration efficiency. Moreover, on the basis of the RP-HPLC and SPR analysis, BHQ was demonstrated to regulate HD1s specific affinity to target molecule with 3-fold photolysis sensitivity and about 40% percent higher uncaging efficiency than Bhc (6-bromo-7-hydroxycoumarin-4-ylmethyl) group. It was proposed that the development and use of quinoline derivative may provide a general strategy to photo-regulate oligonucleotide's activity with improved caging and uncaging efficiencies by the convenient non-site-specific caging method.