A Small-Molecule Probe with a Dual Function of miRNA Inhibition and Target identification.

By virtue of their key roles in pathologies, miRNAs represent a promising class of therapeutic targets. While high-fidelity small-molecule modulators of miRNAs can be identified via high-throughput screening using cellular reporter systems, their modes of action are elusive due to the lack of proper tools. Here, we report a small-molecule probe, 1 a, that is capable of elucidating its biological target along miRNA inhibition.

Metal- and Strain-Free Bioorthogonal Cycloaddition of o-Diones with Furan-2(3H)-one as Anionic Cycloaddend.

The development of new bioorthogonal reactions with mutual orthogonality to classic bioorthogonal reactions such as the strain-promoted azide-alkyne click reaction and the inverse-electron-demand Diels-Alder reaction is of great importance in providing chemical tools for multiplex labelling of live cells. Here we report the first anionic cycloaddend-promoted bioorthogonal cycloaddition reaction between phenanthrene-9,10-dione and furan-2(3H)-one derivatives, where the high polarity of water is exploited to stabilize the highly electron-rich anionic cycloaddend. The reaction is metal- and strain-free, which proceeds rapidly in aqueous solution and on live cells with a second-order rate constant up to 119 M  s .