Conformation and proton configuration of pyrimidine deoxynucleoside oxidation damage products in water

Christopher J. La Francois, Yun Hee Jang, Tahir Cagin, William A. Goddard, Lawrence Sowers

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Emerging data strongly suggest that the oxidation of DNA bases can contribute to genomic instability. Structural changes to DNA, induced by base oxidation, may reduce the fidelity of DNA replication and interfere with sequence-specific DNA-protein interactions. We have examined the structures of a series of pyrimidine deoxynucleoside oxidation damage products in aqueous solution. The modified nucleosides studied include the deoxynucleoside derivatives of 5-hydroxyuracil, 5-hydroxycytosine, 5- (hydroxymethyl)uracil, 5-(hydroxymethyl)cytosine, 5-formyluracil, and 5- formylcytosine. The influence of base oxidation on ionization constants, sugar conformation, and tautomeric configuration has been determined on the basis of UV, proton, and nitrogen NMR spectra of the 15N-enriched derivatives. The potential biological consequences of the structural perturbations resulting from base oxidation are discussed.

Original languageEnglish (US)
Pages (from-to)462-470
Number of pages9
JournalChemical Research in Toxicology
Volume13
Issue number6
DOIs
StatePublished - Jun 2000
Externally publishedYes

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Conformations
Protons
Oxidation
Uracil
Water
Genomic Instability
Cytosine
DNA
DNA Replication
Nucleosides
Nitrogen
Derivatives
Proteins
Sugars
Ionization
Nuclear magnetic resonance
pyrimidine
5-formylcytosine
5-formyluracil
5-hydroxycytosine

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Conformation and proton configuration of pyrimidine deoxynucleoside oxidation damage products in water. / La Francois, Christopher J.; Jang, Yun Hee; Cagin, Tahir; Goddard, William A.; Sowers, Lawrence.

In: Chemical Research in Toxicology, Vol. 13, No. 6, 06.2000, p. 462-470.

Research output: Contribution to journalArticle

La Francois, Christopher J. ; Jang, Yun Hee ; Cagin, Tahir ; Goddard, William A. ; Sowers, Lawrence. / Conformation and proton configuration of pyrimidine deoxynucleoside oxidation damage products in water. In: Chemical Research in Toxicology. 2000 ; Vol. 13, No. 6. pp. 462-470.
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