Novel Convenient Approach to the Solid-Phase Synthesis of Oligonucleotide Conjugates

Abstract

A novel and convenient approach for the solid-phase 5'-functionalization of oligonucleotides is proposed in this article. The approach is based on the activation of free 5'-hydroxyl of polymer support-bound protected oligonucleotides by <i>N</i>,<i>N</i>'-disuccinimidyl carbonate followed by interaction with amino-containing ligands. Novel amino-containing derivatives of <i>closo</i>-dodecaborate, estrone, cholesterol, and α-tocopherol were specially prepared. A wide range of oligonucleotide conjugates bearing <i>closo</i>-dodecaborate, short peptide, pyrene, lipophilic residues (cholesterol, α-tocopherol, folate, estrone), aliphatic diamines, and propargylamine were synthesized and characterized to demonstrate the versatility of the approach. The developed method is suitable for the conjugate synthesis of oligonucleotides of different types (ribo-, deoxyribo-, 2'-<i>O</i>-methylribo-, and others).