3′-Oligonucleotides conjugation via chemoselective oxime bond formation

Chemoselective oxime ligation of cyclopeptide, fluorescein and mannose derivatives at the 3′-end of an oligonucleotide was achieved. The conjugation was performed by reacting oxyamine containing reporter groups to an oligonucleotide bearing an aldehyde at the 3′-extremity. The aldehyde was generated by mild periodate oxidation of a 1,2-aminoalcohol which was readily incorporated at the 3′-end by automated DNA synthesis using the corresponding commercially available support. The straightforward chemical access, their stability in biological media as well as their unchanged hybridisation properties emphasise the interest of such 3′-conjugates.