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 metalbased 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 H NPP was devised for the site-specific binding of copper(II) ions upon irradiation by light, based on the ligand 3hydroxy-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 H NPP :H NPP or H NPP :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.

Modulating aptamer function by copper(ii)-mediated base pair formation

“…30,31 Likewise, the formation of metal-mediated base pairs was applied to regulate the activity of nucleic acids such as DNAzymes or aptamers. 27–29,32–35…”

“…25,26 Even metal-mediated base pairs whose formation is triggered by light irradiation were reported. [27][28][29] Recently, a metal-responsive structural transformation was achieved using metal-mediated base pairs, allowing switching between different nucleic acid topologies. 30,31 Likewise, the formation of metal-mediated base pairs was applied to regulate the activity of nucleic acids such as DNAzymes or aptamers.…”

“…30,31 Likewise, the formation of metal-mediated base pairs was applied to regulate the activity of nucleic acids such as DNAzymes or aptamers. [27][28][29][32][33][34][35] Based on our recent report on using Ag(I)-mediated base pair formation to modulate the activity of an ATP aptamer, 35 we set out to expand the scope of metal-mediated base pairing in modulating aptamer function. Towards this end, an artificial nucleoside capable of forming Cu(II)-mediated base pairs was introduced into two different aptamers, namely the ATPbinding aptamer investigated previously in the context of Ag(I)mediated base pairing and an arginine-binding aptamer.…”

Benzothiazole-substituted 1,3-diaza-2-oxophenoxazine as a luminescent nucleobase surrogate for silver(i)-mediated base pairing

“…[25][26][27] Interestingly, the formation of metal-mediated base pairs can also be used to generate oligonucleotides responsive to external triggers. [28][29][30][31][32][33][34] With an appropriate number and orientation of donor atoms, some ligand-based artificial nucleosides are able to coordinate more than one metal ion, forming polynuclear metal-mediated base pairs. The stability of these structures can be limited by an increased positive charge density due to the close arrangement of metal cations, resulting in repulsive interactions.…”

“…25–27 Interestingly, the formation of metal-mediated base pairs can also be used to generate oligonucleotides responsive to external triggers. 28–34…”