Chemical and photoinduced interstrand crosslinking of oligo DNA duplexes containing 2′-deoxythioguanosines

Interstrand crosslinked nucleic acids offer diverse applications, including stabilizing DNA nanostructures in nanotechnology, enhancing miRNA inhibition in therapeutics, and studying enzyme activity in biochemistry. In this study, we present a new crosslinking design strategy that incorporates two 2'-deoxythioguanosine residues at noncomplementary yet strategically proximal positions within an oligo DNA duplex, promoting efficient disulfide crosslinking under chemical oxidation conditions. Additionally, this approach enables a photoinduced crosslinking reaction using 365 nm UV light, further facilitating the formation of disulfide crosslinked duplex. Our results demonstrate that the proximity of reactive thiocarbonyl groups of 2'-deoxythioguanosines incorporated within the duplex favors disulfide bond formation. Herein, we report the design strategy, crosslinking reaction results, and characterization of the crosslinked product. Furthermore, we introduce a new photoinduced disulfide crosslinking reaction and elucidate its mechanism.