The phosphorothioate (PS) linkage has been widely utilized in oligonucleotide therapeutics.However, they are known to partially desulfurize during the cleavage and deprotection (C&D) step and could cause quality-control problems.<\/p>\n\n\n\n
The purification of these impurities is quite difficult because they have physical properties similar to those of their intact counterparts. <\/p>\n\n\n\n
Therefore, we developed a robust C&D method that suppresses the desulfurization of PS-modified oligonucleotides. As a result, we found that the desulfurization can be avoided by adding reducing inorganic salts to the reaction solutions.<\/p>\n\n\n\n
Our method showed more effective inhibition of sulfur loss than the conventional method. In addition, this method also strongly reduced sulfur loss even under various severe conditions.<\/p>\n\n\n\n
This new C&D method has potential application for manufacturing high-quality oligonucleotide drug substances.<\/p>\n\n\n\n