1024011-87-7Relevant academic research and scientific papers
Utility of 5'-o-2,7-dimethylpixyl for solid-phase synthesis of oligonucleotides containing acid-sensitive 8-aryl-guanine adducts
Sproviero, Michael,Rankin, Katherine M.,Witham, Aaron A.,Manderville, Richard A.
, p. 692 - 699 (2014/04/03)
To study the structural and biological impact of 8-aryl-2'-deoxyguanosine adducts, an efficient protocol is required to incorporate them site-specifically into oligonucleotide substrates. Traditional phosphoramidite chemistry using 5'- O-DMT protection can be limiting because 8-aryl-dG adducts suffer from greater rates of acid-catalyzed depurination than dG and are sensitive to the acidic deblock conditions required to remove the DMT group. Herein we show that the 5'-O-2,7- dimethylpixyl (DMPx) protecting group can be used to limit acid exposure and improve DNA synthesis efficiency for DNA substrates containing 8-aryl-dG adducts. Our studies focus on 8-aryl-dG adducts with 8-substituents consisting of furyl (FurdG), phenyl (PhdG), 4-cyanophenyl (CNPhdG), and quinolyl (QdG). These adducts differ in ring size and sensitivity to acid-promoted deglycosylation. A kinetic study for adduct hydrolysis in 0.1 M aqueous HCl determined that FurdG was the most acid-sensitive (55.2-fold > dG), while QdG was the most resistant (5.6-fold > dG). The most acid-sensitive FurdG was chosen for optimization of solid-phase DNA synthesis. Our studies show that the 5'-O-DMPx group can provide a 4-fold increase in yield compared to 5'- O-DMT for incorporation of FurdG into DNA substrates critical for determining adduct impact on DNA synthesis and repair.
Concerning the hydrolytic stability of 8-aryl-2′-deoxyguanosine nucleoside adducts: Implications for abasic site formation at physiological pH
Schlitt, Katherine M.,Sun, Ke-Wen M.,Paugh, Robert J.,Millen, Andrea L.,Navarro-Whyte, Lex,Wetmore, Stacey D.,Manderville, Richard A.
experimental part, p. 5793 - 5802 (2009/12/26)
(Chemical Equation Presented) Direct addition of aryl radical species to the C8-site of 2′-deoxyguanosine (dG) affords C 8-aryl-dG adducts that are produced by carcinogenic arylhydrazines, polycyclic aromatic hydrocarbons (PAHs), and
Oxidation of a biomarker for phenol carcinogen exposure: Expanding the redox chemistry of 2 -deoxyguanosine
Weishar, Jennifer L.,McLaughlin, Christopher K.,Baker, Michael,Gabryelski, Wojciech,Manderville, Richard A.
supporting information; experimental part, p. 1839 - 1842 (2009/04/10)
A biomarker for phenolic carcinogen exposure, 8-(4 -hydroxyphenyl)-2 -deoxyguanosine, has been found to undergo oxidative coupling in the presence of Na2lrCl6 to afford ortho-ortho C-C-coupled polyphenols through the Intermedlacy of
