2Omethylribose

2'-O-methylribose is a five-carbon sugar derived from ribose in which the hydroxyl group at the 2' position is replaced by a methoxy group (–O–CH3). It is the sugar component of 2'-O-methyl nucleosides and is used in various RNA-related contexts, including natural RNA modifications and synthetic oligonucleotides.

Chemically, 2'-O-methylribose retains the D-ribose configuration and forms a furanose ring. The 2' methoxy substituent influences the sugar’s preferred conformation, typically biasing the sugar toward the C3'-endo (north) pucker that is associated with RNA-like A-form geometry in duplexes. This conformational preference can affect base-pairing geometry and overall nucleic acid stability.

Occurrence and use vary by context. In biology, 2'-O-methyl ribose is found as a post-transcriptional modification in certain RNAs, such as some small nuclear RNAs and ribosomal RNA, where 2'-O-methyl residues contribute to RNA stability and function. In synthetic biology and therapeutic development, 2'-O-methylribose is used to produce 2'-O-methyl RNA, a class of nucleic acids in which the 2' hydroxyl is replaced by a methoxy group. These modifications enhance nuclease resistance and binding affinity to complementary RNA, properties advantageous for antisense oligonucleotides and certain small interfering RNAs.

Chemically, 2'-O-methyl nucleosides are accessible through established nucleoside synthesis and protection strategies, enabling incorporation into oligonucleotides via standard phosphoramidite chemistry. The modification is valued for increasing stability and modulating biological activity without drastically altering base recognition. See also references on 2'-O-methyl RNA and ribose chemistry.