Synthesis of Oligoribonucleic Acid Conjugates Using a Cyclooctyne Phosphoramidite

Abstract

The conjugation of a ribonucleic acid 16-mer with the cationic amphiphilic peptide penetratin and an anionic hyaluronan tetrasaccharide by means of Cu-free "click" chemistry is reported. The alkyne-functionalized 16-mer was prepared by automated solid-phase synthesis, using a newly developed strained cyclooctyne phosphoramidite in the final coupling. Cycloaddition of the alkyne functionalized RNA to the azide containing biomolecules led to a clean conversion into the corresponding nucleic acid conjugates.