Alkyne-linked reduction-activated protecting groups for diverse functionalization on the backbone of oligonucleotides

Publication date: Available online 17 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Hisao Saneyoshi, Kazuhiko Kondo, Koichi Iketani, Akira Ono
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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