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Alkyne-linked reduction-activated protecting groups for diverse functionalization on the backbone of oligonucleotides
Hisao Saneyoshi1, Kazuhiko Kondo1, Koichi Iketani1
1Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan.
Abstract:
A versatile conjugatable/bioreduction-responsive protecting group for phosphodiester moieties was designed, synthesized and incorporated into oligonucleotide strands. Subsequently, controlled pore glass-supported oligonucleotides were conjugated to a variety of functional molecules using a copper-catalyzed azide-alkyne cycloaddition reaction. The functionalized protecting groups were deprotected by a nitroreductase/NADH reduction system to give "naked" oligonucleotides. This method allowed the synthesis of oligonucleotide prodrugs bearing the functionalized protecting group at the desired sites and desired residues on oligodeoxyribonucleotide (ODN) backbones.
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