Postsynthetic On-Column 2′ Functionalization of RNA by Convenient Versatile Method

We report a universal straightforward strategy for the chemical synthesis of modified oligoribonucleotides containing functional groups of different structures at the 2 ' position of ribose. The on-column synthetic concept is based on the incorporation of two types of commercial nucleotide phosphoramidites containing orthogonal 2 '-O-protecting groups, namely 2 '-O-thiomorpholine-carbothioate (TC, as permanent) and 2 '-O-tert-butyl(dimethyl)silyl (tBDMS, as temporary), to RNA during solid-phase synthesis. Subsequently, the support-bound RNA undergoes selective deprotection and follows postsynthetic 2 ' functionalization of the naked hydroxyl group. This convenient method to tailor RNA, utilizing the advantages of solid phase approaches, gives an opportunity to introduce site-specifically a wide range of linkers and functional groups. By this strategy, a series of RNAs containing diverse 2 ' functionalities were synthesized and studied with respect to their physicochemical properties.