Cu II -mediated stabilisation of DNA duplexes bearing consecutive ethenoadenine lesions and its application to a metal-responsive DNAzyme.

Metal-mediated nucleobase pairing can play a central role in the expression of metal-responsive DNA functions. We report the Cu-mediated stabilisation of DNA duplexes bearing damaged nucleobases, 1,-ethenoadenine (εA), as metal-binding sites, which was utilised to construct a metal-responsive DNAzyme. Consecutive incorporation of three or more εA-εA mismatch pairs allowed for Cu-dependent significant duplex stabilisation through metal-mediated εA-Cu-εA base pairing. Subsequently, a split DNAzyme with three εA-Cu-εA base pairs was strategically designed. The activity of the εA-modified DNAzyme was enhanced by 5.3-fold upon addition of Cu ions. This study demonstrates the utility of εA lesions for building metal-responsive DNA architectures.