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

作者：Saneyoshi Hisao^*; Kondo Kazuhiko; Iketani Koichi; Ono Akira^*

来源：Bioorganic & Medicinal Chemistry, 2017, 25(13): 3350-3356.

DOI：10.1016/j.bmc.2017.04.020

• Protecting group
• Drug delivery
• Conjugation
• Oligonucleotide therapeutics

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.

• 出版日期2017-7-1