Synthesis, Derivatization and Photochemical Control of an ortho-Functionalized Tetrafluorinated Azobenzene-Modified siRNA

We report the synthesis of an ortho-functionalized tetrafluorinated azobenzene phosphoramidite for its site-specific incorporation into RNA. The tetrafluorinated azobenzene is embedded within the antisense strand of an siRNA duplex to form an ortho-functionalized tetrafluorinated azobenzene-containing siRNA (F-siRNAzo). The F-siRNAzo is inactivated via trans to cis conversion with green light (530 nm), and reactivated with blue light (470 nm) via cis to trans conversion in cell culture. The long half-life and stability of the tetrafluorinated azobenzene unit allows for reversible control of the F-siRNAzo in cell culture for up 72 hours.

Automated summary

We report the synthesis of an ortho-functionalized tetrafluorinated azobenzene phosphoramidite for site-specific incorporation into RNA. The ortho-functionalized tetrafluorinated azobenzene is embedded in the antisense strand of an siRNA duplex to form a modified siRNA. In cell culture, the modified siRNA can be reversibly controlled through photoconversion.