2′-O-[2-[2-(N, N-dimethylamino)ethoxy]ethyl] modified oligonucleotides: Symbiosis of charge interaction factors and stereoelectronic effects

Marija Prhavc, Thazha P. Prakash, George Minasov, P. Dan Cook, Martin Egli*, Muthiah Manoharan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

(Matrix presented) Oligonucleotides with a novel, 2′ -O-[2-[2-(N,N-dimethylamino)ethoxy]ethyl] (2′-O-DMAEOE) modification have been synthesized. This modification, a cationic analogue of the 2′-O-(2-methoxyethyl) (2′-O-MOE) modification, exhibits high binding affinity to target RNA (but not to DNA) and exceptional resistance to nuclease degradation. Analysis of the crystal structure of a self-complementary oligonucleotide containing a single 2′-O-DMAEOE modification explains the importance of charge factors and gauche effects on the observed antisense properties. 2′-O-DMAEOE modified oligonucleotides are ideal candidates for antisense drugs.

Original languageEnglish (US)
Pages (from-to)2017-2020
Number of pages4
JournalOrganic Letters
Volume5
Issue number12
DOIs
StatePublished - Jun 12 2003

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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