An immobilized and reusable Cu(I) catalyst for metal ion-free conjugation of ligands to fully deprotected oligonucleotides through click reaction

Chelation of Cu(I) ions to an immobilized hydrophilic tris(triazolylmethyl)amine chelator on a solid support allowed synthesis of RNA oligonucleotide conjugates from completely deprotected alkyne-oligonucleotides. No oligonucleotide strand degradation or metal ion contamination was observed. Furthermore, use of the immobilized copper(I) ion overcame regioselectivity issues associated with strain-promoted copper-free azide–alkyne cycloaddition.