A MILD AND EFFICIENT SOLID-SUPPORT SYNTHESIS OF NOVEL OLIGONUCLEOTIDECONJUGATES

Conjugates of oligodeoxyribonucleotide phosphorothioate (ODN-PS) with folic acid, retinoic acid, arachidonic acid, and methoxypoly(ethylene glycol)propionic acid have been synthesized. The procedure involved th e initial solid-phase preparation of 5'-amino-functionalized ODN-PS us ing N-pent-4-enoyl-derived (PNT) nucleoside phosphoramidites followed by conjugation of the oligonucleotide either to the ligand acids, usin g 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide as a coupling reagen t, or to their corresponding succinimidyl derivatives. Subsequent expo sure of the support to aqueous ammonium hydroxide (28%, 2 h, 55 degree s C) resulted in the release of the fully deprotected ODN conjugates, which were purified by reversed-phase HPLC or by preparative polyacryl amide gel electrophoresis. The identity of the oligonucleotide conjuga tes was confirmed by MALDI-TOF mass spectral analysis.