DNA Functionality with Photoswitchable Hydrazone Cytidine
A new family of hydrazone modified cytidine phosphoramidite building block was synthesized and incorporated into DNA oligonucleotides to construct photoswitchable DNA strands. The <i>E-Z</i> isomerization triggered by the irradiation of blue light with a wavelength of 450 nm was investigated and confirmed by <sup>1</sup>H NMR and HPLC in the contexts of both nucleoside and DNA oligonucleotide. The light activated <i>Z</i> form isomer of this hydrazone-cytidine with a six-member intramolecular hydrogen bond was found to inhibit DNA synthesis in the primer extension model by using <i>Bst</i> DNA polymerase. In addition, the hydrazone modification caused the misincorporation of dATP together with dGTP into the growing DNA strand with similar selectivity, highlighting the potential G to A mutation. This work provides a novel functional DNA building block and an additional molecular tool that have potential chemical biology and bio-medicinal applications to control DNA synthesis and DNA-enzyme interactions using cell friendly blue light irradiation.