471D

CRYSTAL STRUCTURE AND IMPROVED ANTISENSE PROPERTIES OF 2'-O-(2-METHOXYETHYL)-RNA

Summary for 471D

• Entry DOI: 10.2210/pdb471d/pdb
• Descriptor: RNA (5'-R(*(C43)P*(G48)P*(C43)P*(G48)P*(A44)P*(A44)P*(U36)P*(U36)P*(C43)P*(G48)P*(C43)P*(G48))-3'), MAGNESIUM ION (3 entities in total)
• Functional Keywords: 2'-o-(2-methoxyethyl) ribose, rna dodecamer duplex, ribonucleic acid, rna
• Total number of polymer chains: 2
• Total formula weight: 9097.18

Authors

Teplova, M.,Minasov, G.,Tereshko, V.,Inamati, G.,Cook, P.D.,Egli, M. (deposition date: 1999-04-29, release date: 1999-05-12, Last modification date: 2024-02-28)

Primary citation

Teplova, M.,Minasov, G.,Tereshko, V.,Inamati, G.B.,Cook, P.D.,Manoharan, M.,Egli, M.
Crystal structure and improved antisense properties of 2'-O-(2-methoxyethyl)-RNA.
Nat.Struct.Biol., 6:535-539, 1999

PubMed Abstract: 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.

PubMed: 10360355
DOI: 10.1038/9304

Experimental method

X-RAY DIFFRACTION (2.7 Å)