2'-O-(2-Methoxyethyl)-RNA (MOE-RNA) is a nucleic acid analog with promising features for antisense applications. Compared with phosphorothioate DNA (PS-DNA), the MOE modification offers improved nuclease resistance, enhanced RNA affinity, improved cellular uptake and intestinal absorption, reduced toxicity and immune stimulation. The crystal structure of a fully modified MOE-RNA dodecamer duplex (CGCGAAUUCGCG) was determined at 1.7 A resolution. In the majority of the MOE substituents, the torsion angle around the ethylene alkyl chain assumes a gauche conformation. The conformational preorganization of the MOE groups is consistent with the improved RNA affinity and the extensive hydration of the substituents could play a role in the improved cellular uptake of MOE-RNA. A specific hydration pattern that bridges substituent and phosphate oxygen atoms in the minor groove of MOE-RNA may explain its high nuclease resistance.
Crystal structure and improved antisense properties of 2'-O-(2-methoxyethyl)-RNA.,Teplova M, Minasov G, Tereshko V, Inamati GB, Cook PD, Manoharan M, Egli M Nat Struct Biol. 1999 Jun;6(6):535-9. PMID:10360355
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑ Teplova M, Minasov G, Tereshko V, Inamati GB, Cook PD, Manoharan M, Egli M. Crystal structure and improved antisense properties of 2'-O-(2-methoxyethyl)-RNA. Nat Struct Biol. 1999 Jun;6(6):535-9. PMID:10360355 doi:10.1038/9304