Crystal structure and improved antisense properties of 2'-O-(2- methoxyethyl)-RNA

M. Teplova, G. Minasov, V. Tereshko, G. B. Inamati, P. D. Cook, M. Manoharan*, M. Egli

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

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 Å 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.

Original languageEnglish (US)
Pages (from-to)535-539
Number of pages5
JournalNature Structural Biology
Volume6
Issue number6
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

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