2’-O-Methyl adenosine A is classified as a 2’-O-Methyl RNA monomer. 2’-O-Methyl nucleotides are most commonly used to confer nuclease resistance to an oligo designed for anti-sense, siRNA or aptamer-based research, diagnostic or therapeutic purposes, when specific 2’-OH is not required. Nuclease resistance can be further enhanced by phosphorothiolation of appropriate internucleotide linkages within the oligo.

The hydrogen bonding behavior of a 2’-O-Methyl RNA/RNA base pair is closer to that of an RNA/RNA base pair than a DNA/RNA base pair. Consequently, the presence of 2’-O-Methyl nucleotides improves duplex stability. Indeed, incorporation of a 2’-O-Methyl nucleotide into an anti-sense oligo (resulting in a 2’-O-Methyl RNA/DNA chimeric), lead to a increase in the Tm of its duplex with RNA, relative to that formed by an unmodified anti-sense DNA oligo, of 1.3°C per 2’-O-Methyl RNA residue added (2). Moreover, from a synthesis standpoint, the coupling efficiency of 2’-O-Methyl phosphoramidites are higher than those of RNA monomers, resulting in higher yield of full-length oligos.