Azobenzene C‐Nucleosides for Photocontrolled Hybridization of DNA at Room Temperature

Abstract

Herein, we report the reversible light-regulated destabilization of DNA duplexes by using azobenzene C-nucleoside photoswitches. The incorporation of two different azobenzene residues into DNA and their photoswitching properties are described. These new residues demonstrate a photoinduced destabilization effect comparable to the widely applied D-threoninol-linked azobenzene switch, which is currently the benchmark. The photoswitches presented herein show excellent photoswitching efficiencies in DNA duplexes - even at room temperature - which are superior to commonly used azobenzene-based nucleic acid photoswitches. In addition, these photoswitching residues exhibit high thermal stability and excellent fatigue resistance, thus rendering them one of the most efficient candidates for the regulation of duplex stability with light.

Light Regulation of DNA Minicircle Dimerization by Utilizing Azobenzene C‐Nucleosides

“…Importantly, for the m Azo, MeO‐ m Azo, p ‐pyrAzo and m ‐pyrAzo designs it was irrelevant if the trans to cis isomerization was performed before or after annealing of the two single rings. This is a feature that we had investigated in previous studies and is in contrast to the behavior acyclic linker systems where it is difficult to operate the photoswitch at room temperature once the duplex has been formed.…”

“…Different linker strategies were investigated but very few gained a popularity comparable to the so‐called t Azo linker system . However, its switching performance can still be improved‐especially regarding its operation at room temperature: Recently, azobenzene C ‐nucleosides have been introduced to successfully control the hybridization properties of RNA and DNA …”

“…[22] However,i ts switching performance can still be improved-especially regarding its operation at room temperature: Recently,a zobenzene C-nucleosidesh ave been introduced to successfully control the hybridization properties of RNA [25] and DNA. [26] Those C-nucleosidesm imic naturaln ucleosides and represent ap romisingn ew approach of photocontrol of oligonucleotide dimerization behavior (Figure 1a, mAzo). [27] Since previous studies suggested that the orientation of the nucleosidic linker and the azobenzene in the DNA strand are crucial for its switching capabilities, [25] in this study we additionally introduce am ethoxy-group on the 2'-position of the azobenzene C-nucleoside ( Figure 1a,M eO-mAzo).…”

Stimuli‐Responsive DNA Self‐Assembly: From Principles to Applications

“…The photoisomerization of synthetically incorporated azobenzene moietiesd etermines the stability of adjacent base pairs by p-stacking (favored by the trans isomer with good planarity). [76,77] By applying such ap rinciple,S ugiyama and co-workers demonstrated ap hoto-regulated dimerization of DNA origami monomers (Figure5b). [78] Liu and co-workers employed al ight-inducedo pen and close action of aD NA duplex "lock" to dynamically switch the conformational chirality of aD NA-origami-templated plasmonic nanosystem.…”

siRNAzos: A New Class of Azobenzene‐Containing siRNAs that Can Photochemically Regulate Gene Expression

“…− Work by Asanuma and coworkers have designed photoswitchable DNAs, in which an azobenzene monomer from D‐threinol has been used to control duplex formation . More recently, azobenzene C‐nucleosides has been used to control oligonucleotide hybrid formation of various complexes In another investigation, Tang and co‐workers designed an azobenzene linked dumbbell, and via photoregulation, they were able to control the timing of RNase H‐mediated RNA degradation by antisense oligonucleotides …”