Postsynthetic Conjugation of RNA to Carboxylate and Dicarboxylate Molecules

Carboxylates and dicarboxylates are important phosphate mimics. Herein, we present a simple synthetic route for the preparation of RNA carboxylate/dicarboxylate conjugates, starting from suitably protected NH₂- and COOH-containing molecules that are coupled to the RNA on the solid support. The key point in our method was the use of trimethylsilylethanol (TMSE-OH) protecting group, which is removed simultaneously with the silyl protecting group on the 2′-OH of the RNA ribose (e.g. t-Butyldimethylsilyl) during the final RNA cleavage/deprotection steps. The usefulness of this method was demonstrated by preparing different RNA-phosphate mimics oligos.