Oxidation of guanine by carbonate radicals derived from photolysis of carbonatotetramminecobalt(III) complexes and the pH dependence of intrastrand DNA cross-links mediated by guanine radical reactions

Conor Crean, Young Ae Lee, Byeong Hwa Yun, Nicholas Geacintov, Vladimir Shafirovich

Research output: Contribution to journalArticle

Abstract

The carbonate radical anion CO3•- is a decomposition product of nitrosoperoxycarbonate derived from the combination of carbon dioxide and peroxynitrite, an important biological by product of the inflammatory response. The selective oxidation of guanine in DNA by CO3radicals is known to yield spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) products, and also a novel intrastrand cross-linked product: 5′-d(CCATCG*CT*ACC), featuring a linkage between guanine C8 (G*) and thymine N3 (T*) atoms in the oligonucleotide (Crean et al., Nucleic Acids Res. 2008, 36, 742-755). Involvement of the T-N3 (pKa of N3-H is 9.67) suggests that the formation of 5′-d(CCATCG*CT*ACC) might be pH-dependent. This hypothesis was tested by generating CO3C•- radicals through the photodissociation of carbonatotetramminecobalt(III) complexes by steady-state UV irradiation, which allowed for studies of product yields in the pH 5.0-10.0 range. The yield of 5′-dCCATCG*CT*ACC) at pH 10.0 is ∼45 times greater than at pH 5.0; this is consistent with the proposed mechanism, which requires N3(H) thymine proton dissociation followed by nucleophilic addition to the C8 guanine radical.

Original languageEnglish (US)
Pages (from-to)1985-1991
Number of pages7
JournalChemBioChem
Volume9
Issue number12
DOIs
StatePublished - Aug 12 2008

Fingerprint

Photolysis
Carbonates
Guanine
Thymine
Oxidation
DNA
Photodissociation
Peroxynitrous Acid
Biological Products
Carbon Dioxide
Oligonucleotides
Nucleic Acids
Anions
Byproducts
Protons
Irradiation
Decomposition
Atoms

Keywords

  • Carbonate radicals
  • DNA
  • Hole transfer
  • Kinetics
  • Oxidative damage

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology

Cite this

Oxidation of guanine by carbonate radicals derived from photolysis of carbonatotetramminecobalt(III) complexes and the pH dependence of intrastrand DNA cross-links mediated by guanine radical reactions. / Crean, Conor; Lee, Young Ae; Yun, Byeong Hwa; Geacintov, Nicholas; Shafirovich, Vladimir.

In: ChemBioChem, Vol. 9, No. 12, 12.08.2008, p. 1985-1991.

Research output: Contribution to journalArticle

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