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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
Author(s) -
Crean Conor,
Lee Young Ae,
Yun Byeong Hwa,
Geacintov Nicholas E.,
Shafirovich Vladimir
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800105
Subject(s) - chemistry , guanine , radical , thymine , photochemistry , photodissociation , radical ion , dissociation (chemistry) , nucleobase , dna , medicinal chemistry , stereochemistry , nucleotide , organic chemistry , ion , biochemistry , gene
The carbonate radical anion CO 3 .− is a decomposition product of nitrosoperoxycarbonate derived from the combination of carbon dioxide and peroxynitrite, an important biological byproduct of the inflammatory response. The selective oxidation of guanine in DNA by CO 3 .− radicals 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 (p K a 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 CO 3 .− 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′‐d(CCATCG*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.