title: Synthesis and characterization of 8-methoxy-2'- deoxyadenosine-containing oligonucleotides to probe the syn glycosidic conformation of 2'-deoxyadenosine within DNA.
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 counterparts. 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Eason
authors.forename: D M
authors.initials: DM
authors.lastname: Burkhardt
authors.forename: S J
authors.initials: SJ
authors.lastname: Phillips
authors.forename: D P
authors.initials: DP
authors.lastname: Smith
authors.forename: S S
authors.initials: SS
authors.lastname: David
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D003839:Deoxyadenosines / Q000737:chemistry*; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C098765:8-methoxy-2'-deoxyadenosine; D003839:Deoxyadenosines; D015335:Molecular Probes; D009841:Oligonucleotides; D004247:DNA; C058118:2'-deoxyadenosine