Oligonucleotide Conjugates by Means of Copper-Free Click Chemistry - Expanding the Repertoire of Strained Cyclooctyne Phosphoramidites

A set of four phosphoramidite building blocks containing a strained dibenzocyclooctyne moiety is reported, including one example equipped with a cleavable disulfide linker. Application of these amidites in solid-phase oligonucleotide synthesis yields either 5′- or 3′-cyclooctyne-modified nucleic acids. The strained cyclooctyne-bearing oligonucleotides are used in rapid and clean conjugation reactions with azide-containing (bio)molecules.