Triplex formation by oligonucleotides containing novel deoxycytidine derivatives

Chin Yi Huang, Guixia Bi, Paul S. Miller

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)2606-2613
Number of pages8
JournalNucleic Acids Research
Volume24
Issue number13
DOIs
StatePublished - 1996

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Deoxycytidine
Oligonucleotides
Base Pairing
Circular Dichroism
Nucleosides
Methylation
Hydrogen
Binding Sites
Alkylation
Freezing
Spectrum Analysis
DNA
dimethyl sulfate

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 journalArticle

Huang, Chin Yi ; Bi, Guixia ; Miller, Paul S. / Triplex formation by oligonucleotides containing novel deoxycytidine derivatives. In: Nucleic Acids Research. 1996 ; Vol. 24, No. 13. pp. 2606-2613.
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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.",
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