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

Kentaro Ohno; Daiki Sugiyama; Leo Takeshita; Takashi Kanamori; Yoshiaki Masaki; Mitsuo Sekine; Kohji Seio

doi:10.1016/j.bmc.2017.09.032

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

Bioorg Med Chem. 2017 Nov 1;25(21):6007-6015. doi: 10.1016/j.bmc.2017.09.032. Epub 2017 Sep 21.

Authors

Kentaro Ohno¹, Daiki Sugiyama¹, Leo Takeshita¹, Takashi Kanamori¹, Yoshiaki Masaki¹, Mitsuo Sekine¹, Kohji Seio²

Affiliations

¹ Department of Life Science and Technology, Tokyo Institute of Technology, 4259, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
² Department of Life Science and Technology, Tokyo Institute of Technology, 4259, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan. Electronic address: kseio@bio.titech.ac.jp.

PMID: 28986114
DOI: 10.1016/j.bmc.2017.09.032

Abstract

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.

Keywords: Nitrobenzyl group; Nucleoside triphosphate; Photocaging; RNA polymerase inhibitor; T7-RNA polymerase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
Structure-Activity Relationship
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

Substances

Enzyme Inhibitors
Viral Proteins
Guanosine
bacteriophage T7 RNA polymerase
DNA-Directed RNA Polymerases
Uridine Triphosphate