5,6-Dihydropyrimidine Peroxyl Radical Reactivity in DNA

نویسندگان

  • Joanna Maria N. San Pedro
  • Marc M. Greenberg
چکیده

Nucleobase radicals are a major family of reactive species produced in DNA as a result of oxidative stress. Two such radicals, 5-hydroxy-5,6-dihydrothymidin-6-yl radical (1) and 5,6-dihydrouridin-6-yl radical (5), were independently generated within chemically synthesized oligonucleotides from photochemical precursors. Neither nucleobase radical produces direct strand breaks or alkali-labile lesions in single or double stranded DNA. The respective peroxyl radicals, resulting from O2 trapping, add to 5'-adjacent nucleobases, with a preference for dG. Distal dG's are also oxidatively damaged by the peroxyl radicals. Experiments using a variety of sequences indicate that distal damage occurs via covalent modification of the 5'-adjacent dG, but there is no evidence for electron transfer by the nucleobase peroxyl radicals.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Peroxyl - Radical Reaction of RetinylAcetatein Solution

Retinyl acetate suppressed the free radical-induced oxidation of methyl linoleate. Retinyl acetate was reacted with an alkylperoxyl radical in two solvent systems, methanol and benzene, The alkylperoxyl radical was generated by the thermal decompositien of a free radical initiator, 2 2'-azobis(2,4-dimethylyaleronitrile), at 370C. The reaction products were isolated by HPLC and their structures ...

متن کامل

Kinetic and thermodynamic aspects of the chain-breaking antioxidant activity of ascorbic acid derivatives in non-aqueous media.

Ascorbic acid (vit. C) is a cofactor whose reactivity toward peroxyl and other radical species has a key-role in its biological function. At physiological pH it is dissociated to the corresponding anion. Derivatives of ascorbic acid, like ascorbyl palmitate, are widely employed in food or in cosmetics and pharmaceuticals. While the aqueous chemistry of ascorbate has long been investigated, in n...

متن کامل

Additivity rule holds in the hydrogen transfer reactivity of unsaturated fatty acids with a peroxyl radical: mechanistic insight into lipoxygenase.

A simple additivity rule holds in the hydrogen transfer reactivity of unsaturated fatty acids with cumylperoxyl radical, which is expressed by the additive contributions of the reactivity of active hydrogens from the 1,4-pentadiene subunit and those of the allylic subunit; the kinetic isotope effect on the hydrogen transfer reactions (KIE = 6.1) is significantly smaller than that observed for l...

متن کامل

Reactivity of α-amino-peroxyl radicals and consequences for amine oxidation chemistry.

A comparative theoretical study is presented on the formation and fate of α-amino-peroxyl radicals, recently proposed as important intermediates in the aerobic oxidation of amines. After radical abstraction of the weakly bonded αH-atom in the amine substrate, the α-amino-alkyl radical reacts irreversibly with O(2), forming the corresponding α-amino-peroxyl radical. HO(2)˙-elimination from vario...

متن کامل

Addressing the competitive formation of tandem DNA lesions by a nucleobase peroxyl radical: a DFT-D screening.

The presence of two vicinal single-nucleotide oxidative lesions constitutes a pitfall case for DNA repair. Quantum mechanics calculations are performed to elucidate the formation of peroxyl-bridged adducts, where a purine and a pyrimidine base become covalently tethered. A dispersion-corrected density functional theory (DFT-D) screening along the 32 possible adducts built by a combination of th...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 136  شماره 

صفحات  -

تاریخ انتشار 2014