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Updated: Aug 30, 2026

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
Published on: April 3, 2014
Effect of sugar modifications on the solution stability of nucleoside phosphoramidites
Kosuke Chiba1,2, Junsuke Hayashi1, Ryohei Kajino1
1Research and Development Department, Luxna Biotech Co., Ltd, Suita, Osaka, Japan.
Abstract:
Oligonucleotide therapeutics represent a rapidly advancing class of medicines that has attracted substantial attention in recent years. Phosphoramidites with chemical modifications are essential building blocks for their chemical synthesis. Therefore, a deep understanding about the stability of phosphoramidites is crucial for the manufacturing of oligonucleotide therapeutics. Especially, it is known that the DNA phosphoramidite with isobutyryl protected-guanine nucleobase (dG[iBu]) is unstable in anhydrous solution. In this study, the solution stabilities of dG[iBu] phosphoramidites with sugar modification were evaluated. The sugar-modified phosphoramidites in acetonitrile were found to be more stable than DNA phosphoramidites, probably due to steric hindrance of the modifications at their 2'-position. Moreover, N,N-dimethylformamide and dichloromethane were identified as alternative solvents that could improve stability without affecting the reactivity of phosphoramidites in oligonucleotide synthesis.
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