Strategies for oligoribonucleotide synthesis according to the phosphoramidite method

Advances in oligoribonucleotide synthesis have lagged behind those in oligodeoxyribonucleotide synthesis because of the difficulty in identifying orthogonal protecting groups for the 2'- and 5'-hydroxyls. Adaptation of the phosphoramidite method for DNA synthesis to RNA synthesis has greatly improved our understanding of RNA. It allows site-specific introduction of modified nucleosides to any position in an RNA molecule, as well as introduction of variations at multiple sites in the molecule. This overview discusses issues that are relevant to RNA synthesis by the phosphoramidite approach, including supports used, activation of the ribonucleoside phosphoramidites, and protection of the nucleobase, phosphate, and 2'- and 5'-hydroxyls.