Antisense Phosphorothioate Oligodeoxyribonucleotide Targeted against ICAM-1: Use of I-Linker to Eliminate 3‘-Terminal Phosphorothioate Monoester Formation

Detritylation of a 5‘- O -DMT-2‘-deoxyadenosine moiety attached to solid support under acidic conditions (3% dichloroacetic acid/solvent) leads to depurination during oligonucleotide synthesis. Deprotection followed by reversed phase HPLC purification leads to desired oligonucleotide contaminated with significant levels of 3‘-terminal phosphorothiaote (3‘-TPT) monoester ( n − 1)-mer. However, it is demonstrated that attachment of dA nucleoside through its exocyclic amino group to solid support leads to substantial reduction of 3‘-TPT formation, thereby improving the quality of oligonucleotide synthesized.