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 language | English (US) |
|---|---|
| Pages (from-to) | 890-897 |
| Number of pages | 8 |
| Journal | Nucleic Acids Research |
| Volume | 24 |
| Issue number | 5 |
| State | Published - 1996 |
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ASJC Scopus subject areas
- Genetics
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Synthesis and characterization of 8-methoxy-2′-deoxyadenosine-containing oligonucleotides to probe the syn glycosidic conformation of 2′-deoxyadenosine within DNA. / Eason, Robert G.; Burkhardt, Dawn M.; Phillips, Shirley J.; Smith, David P.; David, Sheila S.
In: Nucleic Acids Research, Vol. 24, No. 5, 1996, p. 890-897.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis and characterization of 8-methoxy-2′-deoxyadenosine-containing oligonucleotides to probe the syn glycosidic conformation of 2′-deoxyadenosine within DNA
AU - Eason, Robert G.
AU - Burkhardt, Dawn M.
AU - Phillips, Shirley J.
AU - Smith, David P.
AU - David, Sheila S.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0029928273&partnerID=8YFLogxK
M3 - Article
C2 - 8600457
AN - SCOPUS:0029928273
VL - 24
SP - 890
EP - 897
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 5
ER -