CuII-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 CuII-mediated stabilisation of DNA duplexes bearing damaged nucleobases, 1,N6-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 CuII-dependent significant duplex stabilisation through metal-mediated ϵA–CuII–ϵA base pairing. Subsequently, a split DNAzyme with three ϵA–CuII–ϵA base pairs was strategically designed. The activity of the ϵA-modified DNAzyme was enhanced by 5.3-fold upon addition of CuII ions. This study demonstrates the utility of ϵA lesions for building metal-responsive DNA architectures.