Modification of the 5′ Terminus of Oligodeoxyribonucleotides for Conjugation with Ligands

Abstract

Ligands can be introduced at the 5′ terminus of an oligonucleotide by adding a linker to the ligand and modifying the 5′ terminus of the oligonucleotide. These are then reacted to give the ligand‐oligonucleotide conjugate. This unit describes the addition of carboxylated and aminoalkylated linkers, and phosphorothioate, phosphate, and masked thiol groups to the 5′ terminus of an oligonucleotide. The addition of linkers to ligands and the final reaction that produces the ligand‐conjugated oligonucleotide are described elsewhere in the series. This approach is particularly useful when there is a limited amount of ligand available, when the ligand is sensitive to chemical conditions required for oligonucleotide deprotection, or when the ligand is weakly soluble in solvents required for phosphoramidite‐ or H‐phosphonate‐mediated oligonucleotide synthesis.