Conjugatable and Bioreduction Cleavable Linker for the 5'-Functionalization of Oligonucleotides

An efficient conjugatable and bioreduction cleavable linker was designed and synthesized for the 5′-terminal ends of oligonucleotides. A phosphoramidite reagent bearing this linker was successfully applied to solid phase synthesis and incorporated at the 5′-terminal ends of oligonucleotides. The controlled pore glass (CPG)-supported oligonucleotides were subsequently conjugated to a diverse range of functional molecules using a CuAAC reaction. The synthesized oligonucleotide conjugates were then cleaved using a nitroreductase/NADH bioreduction system to release the naked oligonucleotides.