Conjugation at the oligonucleotide level based on isoxazole phosphoramidites generated by click chemistry

The versatility of the isoxazole generating nitrile oxide–alkyne Huisgen cycloaddition for provision of chemically modified oligonucleotides has been extended; in a novel approach isoxazole conjugated oligodeoxyribonucleotides have been constructed by phosphoramidite chemistry of isoxazole derivatives previously generated by nitrile oxide–alkyne click chemistry. The conjugation involves manual solid phase synthesis at room temperature in aqueous ethanol and proceeds in high yield.

Graphical abstractThe versatility of Huisgen cycloaddition for provision of DNA-conjugates has been extended; in a novel approach isoxazole conjugated oligodeoxyribonucleotides have been constructed by solid phase phosphoramidite coupling of isoxazole derivatives previously generated by click chemistry.Figure optionsDownload full-size imageDownload as PowerPoint slide