Postsynthetic Modification of DNA Phosphodiester Backbone for Photocaged DNAzyme

Photocaged (photoactivatable) biomolecules are powerful tools for noninvasive control of biochemical activities by light irradiation. DNAzymes (deoxyribozymes) are single-stranded oligonucleotides with a broad range of enzymatic activities. In this work, to construct photocaged DNAzymes, we developed a facile and mild postsynthetic method to incorporate an interesting photolabile modification (thioether-enol phosphate, phenol substituted, TEEP–OH) into readily available phosphorothioate DNA. Upon light irradiation, TEEP–OH transformed into a native DNA phosphodiester, and accordingly the DNAzymes with RNA-cleaving activities were turned “on” from its inactive and caged form. Activation of the TEEP–OH-caged DNAzyme by light was also successful inside live cells.