8-(4''-hydroxyphenyl)-2'-deoxyguanosine | 143084-40-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 8-(4''-hydroxyphenyl)-2'-deoxyguanosine
• 英文别名: 8-(4-hydroxyphenyl)-2'-deoxyguanosine；8-(4''-hydroxyphenyl)-dG；2-amino-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-(4-hydroxyphenyl)-1H-purin-6-one
• CAS: 143084-40-6
• 化学式: C₁₆H₁₇N₅O₅
• 分子量: 359.341
• InChiKey: ZHTMGGJKAPJCAV-HBNTYKKESA-N

物化性质

• 密度：
  1.85±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  155
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-(4''-hydroxyphenyl)-2'-deoxyguanosine 在 ammonium hydroxide 、 双氧水 、 copper diacetate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 3-(2-amino-9-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-8-yl)hexa-2,4-dienedioic acid
  参考文献：
  名称：

  羟基自由基诱导的酚C连接2'-脱氧鸟苷加合物的氧化反应生成邻苯二酚

  摘要：

  酚类毒素会刺激氧化应激，并在2'-脱氧鸟苷（dG）的C8位产生C连接的加合物。我们之前曾报道过，在Na 2 IrCl 6或辣根过氧化物酶（HRP）/ H 2 O 2的存在下，C-连接的加成物8-（4''-羟基苯基）-dG（p -PhOH-dG）发生氧化，生成多聚体通过苯氧基自由基产生的加合物[魏沙尔（2008）组织。来吧 10，1839-1842]。现在，我们报告了p -PhOH-dG与两个自由基生成体系Cu II / H 2 O 2或Fe II -EDTA / H 2 O 2的反应，这些体系用于研究C连接的加成产物的去向。羟基自由基（HO •）的存在。产生自由基的体系促进（i）酚环的羟基化以提供邻苯二酚加合物8-（3″，4″-二羟基苯基）-dG（3″，4″ -DHPh-dG）和（ii）H原子从糖部分提取以产生去糖基化的碱基p -PhOH-G。3″，4″ -DHPh-dG与p的比率-CuOH-G对于Cu

  DOI：

  10.1021/tx200365r
• 作为产物：
  描述：

  2'-脱氧鸟苷 在 N-溴代丁二酰亚胺(NBS) 、 trisodium tris(3-sulfophenyl)phosphine 、 palladium diacetate 作用下， 以 水 、 乙腈 为溶剂， 生成 8-(4''-hydroxyphenyl)-2'-deoxyguanosine
  参考文献：
  名称：

  Fluorescent Properties and Conformational Preferences of C-Linked Phenolic-DNA Adducts

  摘要：

  Phenolic toxins and mutagenic diazoquinones generate C-linked adducts at the C8 site of 2'-deoxyguanosine (dG) through the intermediacy of radical species. We have previously reported the site-specific incorporation of these adducts into oligonucleotides using a postsynthetic palladium-catalyzed cross-coupling strategy [Omumi et al. (2011) J. Am. Chem. Soc. 133, 42-50]. We report here the structural impact of these lesions within two decanucleotide sequences containing either 5'- and 3'-flanking pyrimidines or purines. In the complementary strands, the base opposite (N) the C-linked adduct was varied to determine the possibility of mismatch stabilization by the modified nucleobases. The resulting adducted duplex structures were characterized using UV thermal denaturation studies, circular dichroism, fluorescence spectroscopy, and molecular dynamics (MD) simulations. The experimental data showed the C-linked adducts to destabilize the duplex when base paired with its normal partner C but to increase duplex stability within a G:G mismatch. The stabilization within the G:G mismatch was sequence dependent, with flanking purine bases playing a key role in the stabilizing influence of the adduct. MD simulations showed no large structural changes to the B form double helix, regardless of the (anti/syn) adduct preference. Consideration of H-bonding and stacking interactions derived from the MD simulations together with the thermal melting data and changes in fluorescent emission of the adducts upon hybridization to the complementary strands implied that the C-linked phenolic adducts preferentially adopt the syn-conformation within both duplexes regardless of the opposite base N. Given that biological outcome in terms of mutagenicity appears to be strongly correlated to the conformational preference of the corresponding N-linked C8-dG adducts, the potential biological implications of phenolic C-linked adducts are discussed.

  DOI：

  10.1021/tx200247f

文献信息

• Concerning the Hydrolytic Stability of 8-Aryl-2′-deoxyguanosine Nucleoside Adducts: Implications for Abasic Site Formation at Physiological pH
  作者：Katherine M. Schlitt、Ke-wen M. Sun、Robert J. Paugh、Andrea L. Millen、Lex Navarro-Whyte、Stacey D. Wetmore、Richard A. Manderville

  DOI：10.1021/jo901080w

  日期：2009.8.21

  Direct addition of aryl radical species to the C8-site of 2′-deoxyguanosine (dG) affords C8-aryl-dG adducts that are produced by carcinogenic arylhydrazines, polycyclic aromatic hydrocarbons (PAHs), and certain phenolic toxins. A common property of C8-arylpurine adduction is the accompaniment of abasic site formation. To determine how the C8-aryl moiety contributes to sugar loss, UV−vis spectroscopy

  将芳基自由基种直接加到2'-脱氧鸟苷（dG）的C 8位上可得到C 8-芳基-dG加合物，其由致癌的芳基肼，多环芳烃（PAH）和某些酚类毒素产生。C 8-芳基嘌呤加合的共同性质是无碱基位点形成的伴随。为了确定C 8-芳基部分如何导致糖损失，已使用紫外可见光谱法确定N 7 p K a1值和水解动力学，同时利用密度泛函理论（DFT）计算来探究结构特征和C 8的稳定性带有不同对和邻取代基的-芳基-dG加合物。在所有情况下，将C 8 -芳基-dG加合物采取顺含有强ø构象5 '-H···Ñ 3氢与相对于所述核碱基扭曲芳环键。该加合物经历Ñ 7 -protonation与电离常数和n计算7质子亲和力（PA）值类似于用于dG的测量。水解动力学表明，C 8-芳基-dG核苷加合物比dG更易于酸催化水解，其中带有对位取代基的k 1值为ca。比k 1大90至200倍对于dG，对原加合物的作用仅约。大9至60倍。通
• Postsynthetic Guanine Arylation of DNA by Suzuki−Miyaura Cross-Coupling
  作者：Alireza Omumi、Daniel G. Beach、Michael Baker、Wojciech Gabryelski、Richard A. Manderville

  DOI：10.1021/ja106158b

  日期：2011.1.12

  Direct radical addition reactions at the C-8-site of 2'-deoxyguanosine (dG) can afford C-8-Ar-dG adducts that are produced by carcinogenic arylhydrazines, polycyclic aromatic hydrocarbons, and certain phenolic toxins. Such modified nucleobases are also highly fluorescent for sensing applications and possess useful electron transfer properties. The site-specific synthesis of oligonucleotides containing the C-8-Ar-G adduct can be problematic. These lesions are sensitive to acids and oxidants that are commonly used in solid-phase DNA synthesis and are too bulky to be accepted as substrates for enzymatic synthesis by DNA polymerases. Using the Suzuki-Miyaura cross-coupling reaction, we have synthesized a number of C-8-Ar-G-modified oligonucleotides (dimers, trimers, decamers, and a 15-mer) using a range of arylboronic acids. Good to excellent yields were obtained, and the reaction is insensitive to the nature of the bases flanking the convertible 8-Br-G nucleobase, as both pyrimidines and purines are tolerated. The impact of the C-8-Ar-G lesion was also characterized by electrospray ionization tandem mass spectrometry, UV melting temperature analysis, circular dichroism, and fluorescence spectroscopy. The C-8-Ar-G-modified oligonucleotides are expected to be useful substrates for diagnostic applications and understanding the biological impact of the C-8-Ar-G lesion.
• Oxidation of a Biomarker for Phenol Carcinogen Exposure: Expanding the Redox Chemistry of 2′-Deoxyguanosine
  作者：Jennifer L. Weishar、Christopher K. McLaughlin、Michael Baker、Wojciech Gabryelski、Richard A. Manderville

  DOI：10.1021/ol8004694

  日期：2008.5.1

  A biomarker for phenolic carcinogen exposure, 8-(4 ''-hydroxyphenyl)-2'-deoxyguanosine, has been found to undergo oxidative coupling in the presence of Na2IrCl6 to afford ortho-ortho C - C-coupled polyphenols through the intermediacy of a phenoxyl radical. One can envision using such unique chemistry to oxidatively couple strands of DNA for the generation of new biomaterials. Our results also demonstrate the potential for phenolic adducts of DNA to undergo further oxidation reactions that may contribute to phenol-mediated cytotoxicity and genotoxicity.
• Biomarkers for Phenol Carcinogen Exposure Act as pH-Sensing Fluorescent Probes
  作者：Kewen M. Sun、Christopher K. McLaughlin、Dean R. Lantero、Richard A. Manderville

  DOI：10.1021/ja068416l

  日期：2007.2.1

  Biomarkers for phenolic carcinogen exposure, 8-(4' '-hydroxyphenyl)-2'-deoxypurines, have been found to possess pH-sensitive fluorescent properties. Phenolic ionization constants (pK(a)) establish substituent (sigma(-)) constants of 0.46 for N1-Me-dG and 0.55 for dA. Their fluorescent properties prompted the synthesis of 4 that possesses fluorescent pH sensing in the physiological pH region. Our results demonstrate the potential utility of these adducts for pH sensing within nucleic acids, as well as establishing a basis for phenol-mediated carcinogenesis.