This invention relates to the post-synthetic chemical modification of RNA at the 2-position on the ribose ring via a copper catalyzed Huisgen cycloaddition ("click" chemistry: Kolb, Sharpless Drug Discovery Today 2003, 8, 1128). The invention 1) avoids complex, tedious multi-step syntheses of each desired modified ribonucleoside 2) allows diverse chemical modifications using high-fidelity chemistry that is completely orthogonal to commonly used alkylamino, carboxylate and disulfide linker reactivities 3) allows introduction of functional groups that are incompatible with modern automated solid-phase synthesis of RNA and subsequent cleavage-deprotection steps 4) allows introduction of functional groups useful as targeting ligands and 5) enables high-throughput structure-activity relationship studies on chemically modified RNA in 96-well format.
