Abstract
AbstractBioactive small molecules with photo‐removable protecting groups have provided spatial and temporal control of corresponding biological effects. We present the design, synthesis, computational and experimental evaluation of the first photo‐activatable small‐molecule methyltransferase agonist. By blocking the functional N‐H group on MPCH with a photo‐removable ortho‐nitrobenzyl moiety, we have developed a promising photo‐caged compound that had completely concealed its biological activity. Short UV light exposure of cells treated with that caged molecule in a few minutes resulted in a considerable hypermethylation of m6A modification in transcriptome RNAs, implicating a rapid release of the parent active compound. This study validates for the first time the photo‐activatable small organic molecular concept in the field of RNA epigenetic research, which represents a novel tool in spatiotemporal and cellular modulation approaches.
Published Version
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