Photochemically catalyzed generation of site-specific 8-nitroguanine adducts in DNA by the reaction of long-lived neutral guanine radicals with nitrogen dioxide

Vladimir Shafirovich, Steven Mock, Alexander Kolbanovskiy, Nicholas Geacintov

Research output: Contribution to journalArticle

Abstract

A novel photochemical approach is described for synthesizing site-specific 8-nitro-2′deoxyguanosine (8-nitro-dG) adducts DNA. The method is based on the bimolecular reaction of a neutral, deprotonated guanine radical [G(-H)·] in DNA and nitrogen dioxide (·NO2) radicals. This approach is illustrated using the single-stranded oligodeoxyribonucleotide 5′-d(CCATCGCTACC) dissolved in an aqueous solution of nitrite and bicarbonate anions at pH 7.5. The photochemical synthesis was triggered by the selective photodissociation of persulfate anions to yield SO4·- radical anions by either 308 nm XeCl excimer laser pulses or by a continuous irradiation with 290-340 nm light from a 1000 W Xe lamp. The sulfate radicals formed generate the CO3·- and ·NO2 radicals by one-electron oxidation of the bicarbonate and nitrite anions. In turn, the CO3·- radicals site-selectively generate G(-H)· radicals in DNA that combine with ·NO2 to form 8-nitro-dG lesions in the oligonucleotide. The nitrated oligonucleotides were purified by reversed-phase HPLC techniques and are stable at 4 °C for at least 4 days, but depurinate at ambient temperatures of 23 °C at pH 7 with a half-life of ∼20 h. The nature of the reaction and decomposition products were studied by a combination of ESI and MALDITOF mass spectrometric techniques.

Original languageEnglish (US)
Pages (from-to)591-597
Number of pages7
JournalChemical Research in Toxicology
Volume15
Issue number4
DOIs
StatePublished - 2002

Fingerprint

Nitrogen Dioxide
DNA Adducts
Guanine
Anions
DNA
Bicarbonates
Nitrites
Oligonucleotides
Photodissociation
Excimer Lasers
Oligodeoxyribonucleotides
Excimer lasers
Electric lamps
Half-Life
Laser pulses
High Pressure Liquid Chromatography
Irradiation
Electrons
Decomposition
Light

ASJC Scopus subject areas

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

Cite this

Photochemically catalyzed generation of site-specific 8-nitroguanine adducts in DNA by the reaction of long-lived neutral guanine radicals with nitrogen dioxide. / Shafirovich, Vladimir; Mock, Steven; Kolbanovskiy, Alexander; Geacintov, Nicholas.

In: Chemical Research in Toxicology, Vol. 15, No. 4, 2002, p. 591-597.

Research output: Contribution to journalArticle

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