A New Nucleic Acid Prodrug Responsive to High Thiol Concentration: Synthesis of 2′‐O‐Methyldithiomethyl‐Modified Oligonucleotides by Post‐Synthetic Modification. Issue 1 (15th February 2018)

• Record Type: Journal Article
• Authors: Ochi, Yosuke; Nakagawa, Osamu; Hayashi, Junsuke; Wada, Shun‐ichi; Urata, Hidehito
• Editors: Egli, Martin; Herdewijn, Piet; Matusda, Akira; Sanghvi, Yogesh S.
• Is Part Of: Current protocols in nucleic acid chemistry. Volume 62:Issue 1(2015)
• Page Start: 4.63.1
• Page End: 4.63.20
• Publication Date: 2018-02-15
• Subjects: modified oligonucleotide -- 2, 4, 6‐trimethoxybenzylthiomethyl group -- methyldithiomethyl group -- post‐synthetic modification -- prodrug RNA -- conversion in reducing environment; Nucleic acids -- Laboratory manuals; Nucleic Acids -- chemical synthesis; Nucleic acids; Laboratory Manuals; Electronic books; Laboratory manuals; 572.8028
• DOI: 10.1002/0471142700.nc0463s62
• Languages: English
• ISSNs: 1934-9270

Abstract

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. © 2015 by John Wiley & Sons, Inc.