Conjugation of oligonucleotides via an electrophilic tether: N-chloroacetamidohexyl phosphoramidite reagent.

A novel method for the preparation of oligonucleotides conjugated with nucleophilic ligands is described. A new phosphoramidite building block derived from N-chloroacetyl-6-aminohexanol is attached at the 5'-terminus on the last step of oligonucleotide synthesis. Postsynthetic treatment of support-bound modified oligonucleotide with a variety of amines and mercaptans affords conjugates in high yield.