The development of bioorthogonal reactions have had a transformative impact in chemical biology and the quest to expand this toolbox continues. Herein we review recent applications of ruthenium‐catalyzed photoredox reactions used in chemical biology.
DNA-based circuitry empowers logic gated operations and amplifications but are restricted to a nucleic acid output. Templated reactions enable the translation of a nucleic acid cues into diverse small molecule outputs but are more limited in their amplification. Herein, we demonstrate the coupling of a DNA circuit to templated reactions in order to achieve high levels of amplification in the output of small molecules, in response to a nucleic acid input. We demonstrate that the coupling of the DNA circuit to templated reactions allow for the detection of fM concentration of analyte and can respond with the release of a cytotoxic drug.
Bioluminescence resonance energy transfer (BRET) is extensively used to study dynamic systems and has been utilized in sensors for studying protein proximity, metabolites, and drug concentrations. Herein, we demonstrate that BRET can activate a ruthenium-based photocatalyst which performs bioorthogonal reactions. BRET from luciferase to the ruthenium photocatalyst is used to uncage effector molecules with up to 64 turnovers of the catalyst, achieving concentrations >0.6 μM effector with 10 nM luciferase construct. Using a BRET sensor, we further demonstrate that the catalysis can be modulated in response to an analyte, analogous to allosterically controlled enzymes. The BRET-induced reaction is used to uncage small-molecule drugs (ibrutinib and duocarmycin) at biologically effective concentrations in cellulo.
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