A new family of hydrazone modified cytidine phosphoramidite building block was synthesized and incorporated into oligodeoxynucleotides to construct photoswitchable DNA strands. The E-Z isomerization triggered by the irradiation of blue light with a wavelength of 450 nm was investigated and confirmed by 1 H NMR spectroscopy and HPLC in the contexts of both nucleoside and oligodeoxynucleotide. The light activated Z 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 Bst DNA polymerase. In addition, the hydrazone modification caused the misincorporation of dATP together with dGTP into the growing DNA strand with similar selectivity, highlighting a potential G to A mutation. This work provides a novel functional DNA building block and an additional molecular tool that has potential chemical biology and biomedicinal applications to control DNA synthesis and DNA-enzyme interactions using the cell friendly blue light irradiation.
Keywords: DNA function; DNA synthesis; hydrazone photoswitch; photoregulation; solid phase synthesis.
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