Synthesis and miscoding specificity of oligodeoxynucleotide containing 8-phenyl-2'-deoxyguanosine

Chemical Research in Toxicology
K KohdaShinya Shibutani

Abstract

Aryl radicals and arenediazonium ions are suspected to react with cellular DNA, resulting in C8-arylguanine adducts. 8-Phenyl-2'-deoxyguanosine (8-PhdG) was synthesized as a model adduct by reacting dG with benzenediazonium chloride and incorporated into oligodeoxynucleotides using phosphoramidite techniques. A site-specifically modified oligodeoxynucleotide containing a single 8-PhdG was then used as a template for primer extension reactions catalyzed by the intact (exo+) or 3'-->5' exonuclease-free (exo-) Klenow fragment of Escherichia coli DNA polymerase I and mammalian DNA polymerase alpha (pol alpha). Although primer extensions catalyzed by the Klenow fragments were retarded at the position of 8-PhdG, most of the primer extension passed the lesion to form the fully extended products. In contrast, primer extensions catalyzed by pol alpha were strongly blocked opposite the lesion. The fully extended products formed during DNA synthesis were analyzed to quantify the miscoding specificities of 8-PhdG. The exo- Klenow fragment incorporated primarily dCMP, the correct base, opposite 8-PhdG, along with small amounts of incorporation of dAMP. Two-base deletions were also observed. In contrast, the exo+ Klenow fragment incorporated...Continue Reading

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Citations

Dec 13, 2007·Chemical Research in Toxicology·James C Delaney, John M Essigmann
Aug 22, 2006·Nucleic Acids Research·M Thomas P GilbertStephan C Schuster
Nov 2, 2016·Chemical Research in Toxicology·Richard A Manderville, Stacey D Wetmore
Mar 14, 2018·Organic & Biomolecular Chemistry·V Vongsutilers, P M Gannett
Jan 5, 2019·Chemical Society Reviews·François-Xavier Felpin, Saumitra Sengupta
Nov 16, 2007·Chemical Communications : Chem Comm·Igor CernaMichal Hocek
Aug 3, 2005·Journal of Biomolecular Structure & Dynamics·Sue Heavner, Peter M Gannett
Nov 12, 2010·Journal of the American Chemical Society·Alireza OmumiRichard A Manderville
Sep 13, 2011·Chemical Research in Toxicology·Alireza OmumiRichard A Manderville
Jun 19, 2014·Chemical Research in Toxicology·Katie A Wilson, Stacey D Wetmore
Aug 24, 2017·Journal of Agricultural and Food Chemistry·Richard A Manderville, Stacey D Wetmore
Aug 16, 2003·The Journal of Organic Chemistry·Elizabeth C WesternKevin H Shaughnessy
May 12, 2006·The Journal of Physical Chemistry. a·Christopher K McLaughlinRichard A Manderville

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