Synthesis and characterization of 8-methoxy-2′-deoxyadenosine-containing oligonucleotides to probe the syn glycosidic conformation of 2′-deoxyadenosine within DNA

Robert G. Eason, Dawn M. Burkhardt, Shirley J. Phillips, David P. Smith, Sheila S. David

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The synthesis of 8-methoxy-2′-deoxyadenosine (moA) protected at N6 as an N,N-dimethylformamidine derivative and incorporation of the modified nucleoside into oligodeoxynucleotides via the phosphoramidite method are described. UV thermal denaturation studies were conducted on duplexes containing moA:G, moA:C and moA:T base pairs to determine the thermodynamic stability of duplexes containing moA relative to their adenosine (A)-containing counter-parts. In the case of moA:G base pairs the effect of moA substitution is sequence dependent. In A:G mismatch-containing sequences, which have been shown by structural characterization to have a syn conformational preference at the glycosidic bond of A, moA substitution results in stabilization of the duplex. In contrast, in sequences where the A in the A:G mismatch has been shown to prefer the anti conformation moA substitution is destabilizing to the duplex. Thus moA may be a useful probe for investigating the conformational preferences of the N-glycosidic bond of adenosine within DNA. In addition, moA nucleoside is more resistant to acid-catalyzed depurination than previously described 8-bromo-2′-deoxyadenosine, allowing for facile incorporation into oligonucleotides via automated solid phase DNA synthesis.

Original languageEnglish (US)
Pages (from-to)890-897
Number of pages8
JournalNucleic Acids Research
Volume24
Issue number5
StatePublished - 1996

ASJC Scopus subject areas

  • Genetics

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