Efficient Synthesis of DNA Conjugates by Strain-Promoted Azide-Cyclooctyne Cycloaddition in the Solid Phase

Conjugation of ligands to DNA oligonucleotides has been achieved in the solid phase by strain-promoted azide-alkyne cycloaddition (SPAAC). The oligonucleotide, modified with a simple nonfluroinated, monocyclic octyne, efficiently forms conjugates with a range of azide dipoles with varying steric and electronic characteristics. The reaction is clean and easily executed in a copper free environment at room temperature. It provides a variety of triazole-linked nucleic acid conjugates and is potentially useful in biotechnology and cell biology.