Chemical phosphorylation of deoxyribonucleosides and thermolytic DNA oligonucleotides.
The phosphorylating reagent bis[S-(4,4'-dimethoxytrityl)-2-mercaptoethyl]-N,N-diisopropylphosphoramidite is prepared in three steps from commercial methyl thioglycolate and diisopropylphosphoramidous dichloride. The phosphorylating reagent has been used successfully in the solid-phase synthesis of deoxyribonucleoside 5'-/3'-phosphate or -thiophosphate monoesters and oligonucleotide 5'-phosphate/-thiophosphate monoesters. Bis[S-(4,4'-dimethoxytrityl)-2-mercaptoethyl]-N,N-diisopropylphosphoramidite has also been employed in the construction of a thermolytic dinucleotide prodrug model to evaluate the ability of the reagent to produce thermosentive oligonucleotide prodrugs under mild temperature conditions ( approximately 25 degrees C) for potential therapeutic applications.
Ausín
Cristina
C
Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA.
Grajkowski
Andrzej
A
Cieślak
Jacek
J
Beaucage
Serge L
SL
D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D003853:Deoxyribonucleosides / Q000737:chemistry*; D010766:Phosphorylation
D003853:Deoxyribonucleosides; D004247:DNA