Mechanistic Investigation on ROS Resistance of Phosphorothioated DNA

Phosphorothioated DNA (PT-DNA) exhibits a mild anti-oxidant property both in vivo and in vitro . It was found that 8-OHdG and ROS levels were significantly lower in dnd + (i.e. S + ) E. coli. , compared to a dnd − (i.e. S − ) strain. Furthermore, different from traditional antioxidants, phosphorothi...

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Published in:Scientific reports 2017-02, Vol.7 (1), p.42823-42823, Article 42823
Main Authors: Wu, Tingting, Huang, Qiang, Wang, Xiao-Lei, Shi, Ting, Bai, Linquan, Liang, Jingdan, Wang, Zhijun, Deng, Zixin, Zhao, Yi-Lei
Format: Article
Language:English
Subjects:
132/122
631/92/56
8-Hydroxydeoxyguanosine
Antioxidants
Deoxyribonucleic acid
DNA
E coli
Genomes
Guanine
Humanities and Social Sciences
Hydroxyl radicals
Liquid chromatography
Mass spectrometry
Mass spectroscopy
multidisciplinary
Neutralization
Oxidants
Oxidation
Oxidizing agents
Phosphorothioate
Phosphorus
Science
Sulfur
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Summary:Phosphorothioated DNA (PT-DNA) exhibits a mild anti-oxidant property both in vivo and in vitro . It was found that 8-OHdG and ROS levels were significantly lower in dnd + (i.e. S + ) E. coli. , compared to a dnd − (i.e. S − ) strain. Furthermore, different from traditional antioxidants, phosphorothioate compound presents an unexpectedly high capacity to quench hydroxyl radical. Oxidative product analysis by liquid chromatography-mass spectrometry and quantum mechanistic computation supported its unique anti-oxidant characteristic of the hydroxyl selectivity: phosphorothioate donates an electron to either hydroxyl radical or guanine radical derived from hydroxyl radical, leading to a PS • radical; a complex of PS • radical and OH − (i.e. the reductive product of hydroxyl radical) releases a highly reductive HS • radical, which scavenges more equivalents of oxidants in the way to high-covalent sulphur compounds such as sulphur, sulphite and sulphate. The PS-PO conversion (PS and PO denote phosphorus-sulphur and phosphorus-oxygen compounds, respectively) made a switch of extremely oxidative OH • to highly reductive HS • species, endowing PT-DNA with the observed high capacity in hydroxyl-radical neutralization. This plausible mechanism provides partial rationale as to why bacteria develop the resource-demanding PT modification on guanine-neighboring phosphates in genome.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep42823