Preparation of Azido Containing Oligonucleotides Through Diazo Transfer Reaction

The use of diazo transfer reagent, imidazole-1-sulfonyl azide hydrochloride (ISAHC), in the presence of Cu2+ cation enables clean and efficient conversion of aminated oligodeoxyribonucleotides (ODNs) into their azido counterparts under mild conditions. ODNs bearing amino tether either at the 3′, 5′, or any internal position could be modified in this way, thus demonstrating the versatility of this reaction. The method also benefits from the commercial availability or easy access by routine automated DNA synthesis of amino-containing oligodeoxyribonucleotide starting material. Easy access to such azido-modified ODNs is of great interest for conjugation in particular through copper catalyzed 1,3-dipolar cycloaddition (CuAAC reaction). Curr. Protoc. Nucleic Acid Chem. 50:4.50.1-4.50.7. © 2012 by John Wiley & Sons, Inc. Keywords: azide; click-chemistry; conjugation; diazotransfer reaction; Huisgen reaction; Staudinger reaction