Triggering Copper(II)-Mediated Base Pair Formation by Light.

Abstract

Metal-mediated base pairs enable a site-specific incorporation of transition metal ions into nucleic acid structures. The resulting nucleic acid-metal complex conjugates are of interest in the context of functionalized nucleic acids, as they bear metal-based functionality. It is desirable to devise nucleic acids with an externally triggered metal-binding affinity, as this may allow regulating this functionality. Toward this end, a caged deoxyribonucleoside analog HNPP was devised for the site-specific binding of copper(II) ions upon irradiation by light, based on the ligand 3-hydroxy-2-methylpyridin-4(1H)-one (H) and the photocleavable 2-(2-nitrophenyl)propoxy protecting group (NPP). The formation of both H-Cu(II)-H homo base pairs and H-Cu(II)-X hetero base pairs (involving a second artificial deoxyribonucleoside X, based on imidazole-4-carboxylate) was achieved upon irradiation of DNA duplexes bearing the respective HNPP:HNPP or HNPP:X mispairs in the presence of copper(II) ions. The H-Cu(II)-X pair shows an exceptional DNA duplex stabilization of up to 43 °C upon its formation, exceeding that of the H-Cu(II)-H pair. It therefore represents one of the most stabilizing Cu(II)-mediated base pairs reported so far. Our findings expand the scope of light-triggered metal-mediated base pair formation by introducing a copper(II)-binding ligand.