Synthesis of photocaged 6-O-(2-nitrobenzyl)guanosine and 4-O-(2-nitrobenzyl) uridine triphosphates for photocontrol of the RNA transcription reaction

• Published in: Bioorganic & medicinal chemistry 2017-11, Vol.25 (21), p.6007-6015
• Main Authors: Ohno, Kentaro, Sugiyama, Daiki, Takeshita, Leo, Kanamori, Takashi, Masaki, Yoshiaki, Sekine, Mitsuo, Seio, Kohji
• Format: Article
• Language: English
• Subjects: DNA-Directed RNA Polymerases - antagonists & inhibitors; DNA-Directed RNA Polymerases - genetics; DNA-Directed RNA Polymerases - metabolism; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Guanosine - analogs & derivatives; Guanosine - chemical synthesis; Guanosine - pharmacology; Molecular Structure; Nitrobenzyl group; Nucleoside triphosphate; Photocaging; RNA polymerase inhibitor; Structure-Activity Relationship; T7-RNA polymerase; Transcription, Genetic - drug effects; Transcription, Genetic - genetics; Ultraviolet Rays; Uridine Triphosphate - chemical synthesis; Uridine Triphosphate - chemistry; Uridine Triphosphate - pharmacology; Viral Proteins - antagonists & inhibitors; Viral Proteins - genetics; Viral Proteins - metabolism
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2017.09.032

[Display omitted] 6-O-(2-Nitrobenzyl)guanosine and 4-O-(2-nitrobenzyl)uridine triphosphates (NBGTP, NBUTP) were synthesized, and their biochemical and photophysical properties were evaluated. We synthesized NBUTP using the canonical triphosphate synthesis method and NBGTP from 2′,3′-O-TBDMS guanosine via a triphosphate synthesis method by utilizing mild acidic desilylation conditions. Deprotection of the nitrobenzyl group in NBGTP and NBUTP proceeded within 60s by UV irradiation at 365nm. Experiments using NBGTP or NBUTP in T7-RNA transcription reactions showed that NBGTP could be useful for the photocontrol of transcription by UV irradiation.