Abstract
In order to study base pairing properties of the amide group in DNA duplexes, a nucleoside analog, 1-(2'-deoxy-β-D-ribofuranosyl)pyrrole-3-carboxamide, was synthesized by a new route from the ester, methyl 1-(2'-deoxy-3',5'-di-O-p-toluoyl-β-D-erythro-pentofuranosyl)pyrrole 3-carboxylate, obtained from the coupling reaction between 1-chloro-2-deoxy-3,5-di-O-toluoyl-D-erythropentofuranose and methyl pyrrole-3-carboxylate by treatment with dimethylaluminum amide. 1-(2'-Deoxy-β-D-ribofuranosyl)pyrrole-3-carboxamide, was incorporated into a series of oligodeoxyribonucleotides by solid-phase phosphoramidite technology. The corresponding oligodeoxyribonucleotides with 3-nitropyrrole in the same position in the sequence were synthesized for UV comparison of helix-coil transitions. The thermal melting studies indicate that pyrrole-3-carboxamide, which could conceptually adopt either a dA-like or a dI-like hydrogen bond conformation, pairs with significantly higher affinity to T than to dC. Pyrrole-3-carboxamide further resembles dA in the relative order of its base pairing preferences (T > dG > dA > dC). Theoretical calculations on the model compound N-methylpyrrole-3-carboxamide using density functional theory show little difference in the preference for a syn(τ) versus anti(τ) conformation about the bond from pyrrole C3 to the amide carbonyl. The amide groups in both the minimized anti(τ) and syn(τ) conformations are twisted out of the plane of the pyrrole ring by 6-14°. This twist may be one source of destabilization when the amide group is placed in the helix. Another contribution to the difference in stability between the base pairs of pyrrole-3-carboxamide with T and pyrrole-3-carboxamide with C may be the presence of a hydrogen bond in the former involving an acidic proton (N3-H of T).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2208-2215 |
| Number of pages | 8 |
| Journal | Nucleic Acids Research |
| Volume | 26 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
Cite this
Exploratory studies on azole carboxamides as nucleobase analogs : Thermal denaturation studies on oligodeoxyribonucleotide duplexes containing pyrrole-3-carboxamide. / Zhang, Peiming; Johnson, W. Travis; Klewer, Douglas; Paul, Natasha; Hoops, Geoffrey; Davisson, V. J.; Bergstrom, Donald E.
In: Nucleic Acids Research, Vol. 26, No. 9, 01.05.1998, p. 2208-2215.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Exploratory studies on azole carboxamides as nucleobase analogs
T2 - Thermal denaturation studies on oligodeoxyribonucleotide duplexes containing pyrrole-3-carboxamide
AU - Zhang, Peiming
AU - Johnson, W. Travis
AU - Klewer, Douglas
AU - Paul, Natasha
AU - Hoops, Geoffrey
AU - Davisson, V. J.
AU - Bergstrom, Donald E.
PY - 1998/5/1
Y1 - 1998/5/1
N2 - In order to study base pairing properties of the amide group in DNA duplexes, a nucleoside analog, 1-(2'-deoxy-β-D-ribofuranosyl)pyrrole-3-carboxamide, was synthesized by a new route from the ester, methyl 1-(2'-deoxy-3',5'-di-O-p-toluoyl-β-D-erythro-pentofuranosyl)pyrrole 3-carboxylate, obtained from the coupling reaction between 1-chloro-2-deoxy-3,5-di-O-toluoyl-D-erythropentofuranose and methyl pyrrole-3-carboxylate by treatment with dimethylaluminum amide. 1-(2'-Deoxy-β-D-ribofuranosyl)pyrrole-3-carboxamide, was incorporated into a series of oligodeoxyribonucleotides by solid-phase phosphoramidite technology. The corresponding oligodeoxyribonucleotides with 3-nitropyrrole in the same position in the sequence were synthesized for UV comparison of helix-coil transitions. The thermal melting studies indicate that pyrrole-3-carboxamide, which could conceptually adopt either a dA-like or a dI-like hydrogen bond conformation, pairs with significantly higher affinity to T than to dC. Pyrrole-3-carboxamide further resembles dA in the relative order of its base pairing preferences (T > dG > dA > dC). Theoretical calculations on the model compound N-methylpyrrole-3-carboxamide using density functional theory show little difference in the preference for a syn(τ) versus anti(τ) conformation about the bond from pyrrole C3 to the amide carbonyl. The amide groups in both the minimized anti(τ) and syn(τ) conformations are twisted out of the plane of the pyrrole ring by 6-14°. This twist may be one source of destabilization when the amide group is placed in the helix. Another contribution to the difference in stability between the base pairs of pyrrole-3-carboxamide with T and pyrrole-3-carboxamide with C may be the presence of a hydrogen bond in the former involving an acidic proton (N3-H of T).
AB - In order to study base pairing properties of the amide group in DNA duplexes, a nucleoside analog, 1-(2'-deoxy-β-D-ribofuranosyl)pyrrole-3-carboxamide, was synthesized by a new route from the ester, methyl 1-(2'-deoxy-3',5'-di-O-p-toluoyl-β-D-erythro-pentofuranosyl)pyrrole 3-carboxylate, obtained from the coupling reaction between 1-chloro-2-deoxy-3,5-di-O-toluoyl-D-erythropentofuranose and methyl pyrrole-3-carboxylate by treatment with dimethylaluminum amide. 1-(2'-Deoxy-β-D-ribofuranosyl)pyrrole-3-carboxamide, was incorporated into a series of oligodeoxyribonucleotides by solid-phase phosphoramidite technology. The corresponding oligodeoxyribonucleotides with 3-nitropyrrole in the same position in the sequence were synthesized for UV comparison of helix-coil transitions. The thermal melting studies indicate that pyrrole-3-carboxamide, which could conceptually adopt either a dA-like or a dI-like hydrogen bond conformation, pairs with significantly higher affinity to T than to dC. Pyrrole-3-carboxamide further resembles dA in the relative order of its base pairing preferences (T > dG > dA > dC). Theoretical calculations on the model compound N-methylpyrrole-3-carboxamide using density functional theory show little difference in the preference for a syn(τ) versus anti(τ) conformation about the bond from pyrrole C3 to the amide carbonyl. The amide groups in both the minimized anti(τ) and syn(τ) conformations are twisted out of the plane of the pyrrole ring by 6-14°. This twist may be one source of destabilization when the amide group is placed in the helix. Another contribution to the difference in stability between the base pairs of pyrrole-3-carboxamide with T and pyrrole-3-carboxamide with C may be the presence of a hydrogen bond in the former involving an acidic proton (N3-H of T).
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UR - http://www.scopus.com/inward/citedby.url?scp=0032077532&partnerID=8YFLogxK
U2 - 10.1093/nar/26.9.2208
DO - 10.1093/nar/26.9.2208
M3 - Article
C2 - 9547282
AN - SCOPUS:0032077532
VL - 26
SP - 2208
EP - 2215
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 9
ER -