Abstract
Homopurine sequences of duplex DNA are binding sites for triplex-forming oligodeoxyribopyrimidines. The interactions of synthetic duplex DNA targets with an oligodeoxyribopyrimidine containing N4-(6-amino-2-pyridinyl)deoxycytidine (1), a nucleoside designed to interact with a single C·G base pair interruption of the purine target tract, was studied by UV melting, circular dichroism spectroscopy and dimethylsulfate alkylation experiments. Nucleoside 1 supports stable triplex formation at pH 7.0 with formation of a 1·Y·Z triad, where Y·Z is a base pair in the homopurine tract of the target. Selective interaction was observed when Y·Z was C·G, although A·T and, to a lesser extent, T·A and G·C base pairs were also recognized. The circular dichroism spectra of the triplex having a 1·C·G triad were similar to those of a triplex having a C+·G·C triad, suggesting that the overall structures of the two triplexes are quite similar. Removal of the 6-amino group from 1 essentially eliminated triplex formation. Reaction of a triplex having the 1·C·G triad with dimethylsulfate resulted in a 50% reduction of methylation of the G residue of this triad. In contrast, the G of a similar triplex containing a U·C·G triad was not protected from methylation by dimethylsulfate. These results are consistent with a binding mode in which the 6-amino-2-pyridinyl group of 1 spans the major groove of the target duplex at the 1·C·G binding site and forms a hydrogen bond with the O6 of G. An additional stabilizing hydrogen bond could form between the N4 of the imino tautomer of 1 and the N4 amino group of C.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2606-2613 |
| Number of pages | 8 |
| Journal | Nucleic Acids Research |
| Volume | 24 |
| Issue number | 13 |
| DOIs | |
| State | Published - 1996 |
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ASJC Scopus subject areas
- Genetics
Cite this
Triplex formation by oligonucleotides containing novel deoxycytidine derivatives. / Huang, Chin Yi; Bi, Guixia; Miller, Paul S.
In: Nucleic Acids Research, Vol. 24, No. 13, 1996, p. 2606-2613.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Triplex formation by oligonucleotides containing novel deoxycytidine derivatives
AU - Huang, Chin Yi
AU - Bi, Guixia
AU - Miller, Paul S.
PY - 1996
Y1 - 1996
N2 - Homopurine sequences of duplex DNA are binding sites for triplex-forming oligodeoxyribopyrimidines. The interactions of synthetic duplex DNA targets with an oligodeoxyribopyrimidine containing N4-(6-amino-2-pyridinyl)deoxycytidine (1), a nucleoside designed to interact with a single C·G base pair interruption of the purine target tract, was studied by UV melting, circular dichroism spectroscopy and dimethylsulfate alkylation experiments. Nucleoside 1 supports stable triplex formation at pH 7.0 with formation of a 1·Y·Z triad, where Y·Z is a base pair in the homopurine tract of the target. Selective interaction was observed when Y·Z was C·G, although A·T and, to a lesser extent, T·A and G·C base pairs were also recognized. The circular dichroism spectra of the triplex having a 1·C·G triad were similar to those of a triplex having a C+·G·C triad, suggesting that the overall structures of the two triplexes are quite similar. Removal of the 6-amino group from 1 essentially eliminated triplex formation. Reaction of a triplex having the 1·C·G triad with dimethylsulfate resulted in a 50% reduction of methylation of the G residue of this triad. In contrast, the G of a similar triplex containing a U·C·G triad was not protected from methylation by dimethylsulfate. These results are consistent with a binding mode in which the 6-amino-2-pyridinyl group of 1 spans the major groove of the target duplex at the 1·C·G binding site and forms a hydrogen bond with the O6 of G. An additional stabilizing hydrogen bond could form between the N4 of the imino tautomer of 1 and the N4 amino group of C.
AB - Homopurine sequences of duplex DNA are binding sites for triplex-forming oligodeoxyribopyrimidines. The interactions of synthetic duplex DNA targets with an oligodeoxyribopyrimidine containing N4-(6-amino-2-pyridinyl)deoxycytidine (1), a nucleoside designed to interact with a single C·G base pair interruption of the purine target tract, was studied by UV melting, circular dichroism spectroscopy and dimethylsulfate alkylation experiments. Nucleoside 1 supports stable triplex formation at pH 7.0 with formation of a 1·Y·Z triad, where Y·Z is a base pair in the homopurine tract of the target. Selective interaction was observed when Y·Z was C·G, although A·T and, to a lesser extent, T·A and G·C base pairs were also recognized. The circular dichroism spectra of the triplex having a 1·C·G triad were similar to those of a triplex having a C+·G·C triad, suggesting that the overall structures of the two triplexes are quite similar. Removal of the 6-amino group from 1 essentially eliminated triplex formation. Reaction of a triplex having the 1·C·G triad with dimethylsulfate resulted in a 50% reduction of methylation of the G residue of this triad. In contrast, the G of a similar triplex containing a U·C·G triad was not protected from methylation by dimethylsulfate. These results are consistent with a binding mode in which the 6-amino-2-pyridinyl group of 1 spans the major groove of the target duplex at the 1·C·G binding site and forms a hydrogen bond with the O6 of G. An additional stabilizing hydrogen bond could form between the N4 of the imino tautomer of 1 and the N4 amino group of C.
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UR - http://www.scopus.com/inward/citedby.url?scp=0029901452&partnerID=8YFLogxK
U2 - 10.1093/nar/24.13.2606
DO - 10.1093/nar/24.13.2606
M3 - Article
C2 - 8692703
AN - SCOPUS:0029901452
VL - 24
SP - 2606
EP - 2613
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 1362-4962
IS - 13
ER -