Facile solid-phase synthesis of a highly stable poly(ethylene glycol)–oligonucleotide conjugate

Abstract

A novel solid-phase synthesis method for poly(ethylene glycol) (PEG)-oligonucleotide conjugates was developed to increase the stability of therapeutic oligonucleotides such as antisense oligonucleotides and siRNA. A prepared solid phase was pre-installed with PEG to provide oligonucleotides modified with PEG at the 3' terminus. Compared with the conventional liquid-phase synthesis method, the developed solid-phase method is simple and reproducible. PEGylation at the 3' terminus was confirmed to stabilize not only DNA but also RNA more than PEGylation at the 5' terminus, which has been widely used so far.