title: A New Nucleic Acid Prodrug Responsive to High Thiol Concentration: Synthesis of 2'-O-Methyldithiomethyl-Modified Oligonucleotides by Post-Synthetic Modification.
abstract: This unit describes the synthesis of 2'-O-methyldithiomethyluridine-containing oligonucleotides, which can be deprotected to yield the parental oligoribonucleotides under high concentrations of glutathione similar in cytoplasm. The 2'-O-methyldithiomethyl group is sensitive to reductive conditions, so that it is incompatible to 3'-O-phosphoramidite modification in nucleosides. Thus, a novel post-synthetic approach to obtain 2'-O-methyldithiomethyluridine-containing oligonucleotides was developed, in which 2'-O-(2,4,6-trimethoxybenzylthiomethyl)uridine-modified oligonucleotides are readily converted by treatment with dimethyl(methylthio)sulfonium tetrafluoroborate to the 2'-O-methyldithiomethyluridine-modified oligonucleotides. The 2'-O-methyldithiomethyluridine-modified oligonucleotides are readily and cleanly converted to the parental oligonucleotides under high thiol conditions, such as 10 mM glutathione and dithiothreitol.
authors.affiliation: Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ochi
authors.affiliation: Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.|Present address: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawa
authors.affiliation: Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Junsuke
authors.initials: J
authors.lastname: Hayashi
authors.affiliation: Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Shun-Ichi
authors.initials: SI
authors.lastname: Wada
authors.affiliation: Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Urata
mesh_terms: D009696:Nucleic Acids / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D009696:Nucleic Acids; D009841:Oligonucleotides; D013438:Sulfhydryl Compounds
keywords: 2,4,6-trimethoxybenzylthiomethyl group; conversion in reducing environment; methyldithiomethyl group; modified oligonucleotide; post-synthetic modification; prodrug RNA