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 language | English (US) |
|---|---|
| Pages (from-to) | 462-470 |
| Number of pages | 9 |
| Journal | Chemical Research in Toxicology |
| Volume | 13 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2000 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Conformation and proton configuration of pyrimidine deoxynucleoside oxidation damage products in water
AU - La Francois, Christopher J.
AU - Jang, Yun Hee
AU - Cagin, Tahir
AU - Goddard, William A.
AU - Sowers, Lawrence
PY - 2000/6
Y1 - 2000/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034045317&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034045317&partnerID=8YFLogxK
U2 - 10.1021/tx990209u
DO - 10.1021/tx990209u
M3 - Article
C2 - 10858319
AN - SCOPUS:0034045317
VL - 13
SP - 462
EP - 470
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
SN - 0893-228X
IS - 6
ER -