EFFICIENT ASSESSMENT OF MODIFIED NUCLEOSIDE STABILITY UNDER CONDITIONS OF AUTOMATED OLIGONUCLEOTIDE SYNTHESIS: CHARACTERIZATION OF THE OXIDATION AND OXIDATIVE DESULFURIZATION OF 2-THIOURIDINE

• Published in: Nucleosides, nucleotides & nucleic acids Vol. 20; no. 10-11; pp. 1871 - 1879
• Main Author: Sochacka, E.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis Group 31.12.2001
• Subjects: Acetonitriles - chemistry; Carbon Tetrachloride - chemistry; Chromatography, High Pressure Liquid; Hydrogen Peroxide - chemistry; Models, Chemical; Nucleic Acid Denaturation; Oligonucleotides - chemical synthesis; Oligonucleotides - chemistry; Oxygen - metabolism; Sulfur - chemistry; Thiouridine - analogs & derivatives; Thiouridine - chemistry; Time Factors
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1081/NCN-100107198

In order to efficiently assess the chemical stability of modified nucleosides to the reagents and conditions of automated oligonucleotide synthesis, we designed, developed and tested a scheme in which the modified nucleoside, directly attached to a solid support, is exposed to the cyclic chemistry of the instrument. Stability of 2-thiouridine against different oxidizers was investigated. Tertbutyl hydroperoxide (1 M) in anhydrous acetonitrile was a more effective oxidizer for the incorporation of 2-thiouridine into oligonucleotide chains than the same oxidizer in methylene chloride. Carbon tetrachloride/water in the presence of a basic catalyst was superior in maintaining the thiocarbonyl function, but its utility for RNA synthesis has yet to be fully tested, whereas 2-phenylsulfonyloxaziridine was a very efficient reagent for oxidative desulfurization of 2-thiouridine.