¹⁵N₅-2′-deoxyguanosine | 686353-29-7

• 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: ¹⁵N₅-2′-deoxyguanosine
• 英文别名: [15N5]-2'-deoxyguanosine；2'-Deoxyguanosine-15N5；2-(15N)azanyl-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-purin-6-one
• CAS: 686353-29-7
• 化学式: C₁₀H₁₃N₅O₄
• 分子量: 272.211
• InChiKey: YKBGVTZYEHREMT-XOTKZIGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  135
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ¹⁵N₅-2′-deoxyguanosine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 水 、 乙腈 为溶剂， 反应 0.5h， 生成 [2-amino-1,3,7,9-15N₅]-8-bromo-2'-deoxyguanosine
  参考文献：
  名称：

  Identification and Quantification of a Guanine−Thymine Intrastrand Cross-Link Lesion Induced by Cu(II)/H₂O₂/Ascorbate

  摘要：

  Reactive oxygen species (ROS) can be induced by both endogenous and exogenous processes, and they can damage biological molecules including nucleic acids. It was shown that X- or gamma-ray irradiation of aqueous solutions of DNA, during which (OH)-O-center dot is one of the major ROS, can lead to the formation of intrastrand cross-link lesions where the neighboring nucleobases in the same DNA strand are covalently bonded. Previous P-32-postlabeling studies suggested that the intrastrand cross- link lesions may arise from Fenton reaction, which also induces the formation of (OH)-O-center dot; the structures of the proposed intrastrand cross- link lesions, however, have not been determined. Here, we showed for the first time that the treatment of calf thymus DNA with Cu(II)/H2O2/ascorbate could lead to the formation of an intrastrand cross-link lesion, i.e., G boolean AND T, where the C8 of guanine is covalently bonded to the neighboring 3'- thymine through its methyl carbon. LC-MS/ MS quantification results showed dose-responsive formation of G boolean AND T. In addition, the yield of the intrastrand cross- link was approximately 3 orders of magnitude lower than those of commonly observed single-base lesions, that is, 8-oxo-7,8-dihydro-2'- deoxyguanosine, 5-( hydroxymethyl)2'- deoxyuridine, and 5-formyl-2'-deoxyuridine. The induction of intrastrand cross- link lesion in calf thymus DNA by Fenton reagents in vitro suggests that this type of lesion might be formed endogenously in mammalian cells.

  DOI：

  10.1021/tx060025x

文献信息

• Quantitative High-Performance Liquid Chromatography−Electrospray Ionization Tandem Mass Spectrometry Analysis of Bis-<i>N</i>7-Guanine DNA−DNA Cross-Links in White Blood Cells of Cancer Patients Receiving Cyclophosphamide Therapy
  作者：Bhaskar Malayappan、L’Aurelle Johnson、Bei Nie、Dolly Panchal、Brock Matter、Pamala Jacobson、Natalia Tretyakova

  DOI：10.1021/ac902923s

  日期：2010.5.1

  application of the new methodology is demonstrated for DNA extracted from blood of three cancer patients receiving 50−60 mg/kg of intravenous CPA. The highest numbers of G-NOR-G adduct (up to 18 adducts per 106 normal nucleotides) were observed 4−8 h following CPA administration, followed by a gradual decrease over time, probably due to adduct hydrolysis, DNA repair, and white blood cell death. This methodology

  环磷酰胺 (CPA) 是一种广泛用于癌症化疗的 DNA 烷化剂。CPA 代谢活化为磷酰胺芥末和去甲氮芥 (NOR)，它们将 DNA 中鸟嘌呤的 N-7 位烷基化以产生N- [2-( N 7-鸟嘌呤基) 乙基]- N -[2-羟乙基]-胺。 G-NOR-OH) 单加合物和N , N -双 [2-( N 7-鸟嘌呤基) 乙基] 胺交联 (G-NOR-G)。G-NOR-G 交联具有很强的细胞毒性，被认为是 CPA 生物活性的原因。在目前的工作中，同位素稀释高效液相色谱-电喷雾电离（正离子）串联质谱（HPLC-ESI +-MS/MS) 方法被开发用于准确量化人类血液中的 G-NOR-G 加合物。在我们的方法中，从白细胞 (5-20 μg) 提取的 DNA 中加入 [ 15 N 10 ]-G-NOR-G的内标，并进行热水解以从 DNA 中释放 G-NOR-G 加合物骨干。固相萃取后，G-NOR-G 偶联物通过毛细管
• <i>trans</i>,<i>trans</i>-2,4-Decadienal-Induced 1,<i>N</i>²-Etheno-2‘-deoxyguanosine Adduct Formation
  作者：Ana Paula M. Loureiro、Paolo Di Mascio、Osmar F. Gomes、Marisa H. G. Medeiros

  DOI：10.1021/tx000004h

  日期：2000.7.1

  well-known reaction product of epoxy aldehydes with dGuo. Two new diasteroisomeric products, A2-1 and A2-2, 1-¿[3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-5, 9-dihydro-9H-imidazo[2,1-i]purin-9-hydroxy]-7-yl¿-2-one-3-octanol, were isolated and characterized on the basis of their spectroscopic features as 1,N(2)-etheno adducts possessing a carbon side chain with a carbonyl and a hydroxyl group. The proposed

  近年来，已经表征了许多由α，β-不饱和醛或其环氧化物与DNA碱基反应产生的环延伸的DNA加合物。这些加合物可能导致DNA复制过程中的错误编码，如果不加以修复，则会导致可能导致癌症发展的突变。反式，反式-2、4-癸二醛（DDE）是由脂质过氧化内源性形成的高度细胞毒性醛之一。为了评估其DNA的破坏潜力，我们研究了过氧化物存在下DDE与2'-脱氧鸟苷（dGuo）的反应。通过反相HPLC分离出三种稳定的加合物。加合物A1，3-（2-deoxy-beta-D-erythro-pentafuranosyl）-5,9-dihydro-9H-imidazo [2，1-i] purin-9-hydroxy，是1，N（2的互变异构体）-etheno-2'-deoxyguanosine，一种众所周知的环氧醛与dGuo的反应产物。两个新的非对映异构体产物A2-1和A2-2，1-[[3-（2'-脱氧β-D-赤型五呋喃糖基）-5，9-二氢-9H-咪唑[2
• High-Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry for the Detection and Quantitation of Pyrrolizidine Alkaloid-Derived DNA Adducts <i>in Vitro</i> and <i>in Vivo</i>
  作者：Peter P. Fu、Ming W. Chou、Mona Churchwell、Yuping Wang、Yuewei Zhao、Qingsu Xia、Gonçalo Gamboa da Costa、M. Matilde Marques、Frederick A. Beland、Daniel R. Doerge

  DOI：10.1021/tx900402x

  日期：2010.3.15

  lizine (DHP)-derived DNA adducts that are responsible for tumor induction. The identification and quantitation of the DHP-derived DNA adducts formed in vivo and in vitro were accomplished previously by 32P-postlabeling/HPLC methodology. In this article, we report the development of a sensitive and specific liquid chromatography−electrospray ionization−tandem mass spectrometry (HPLC-ES-MS/MS) method

  含吡咯烷定生物碱的植物在世界范围内广泛存在，可能是影响牲畜，野生动植物和人类的最常见的有毒植物。吡咯嗪核生物碱需要代谢才能发挥其遗传毒性和致瘤性。我们已经确定，在体外或体内一系列致瘤的吡咯烷核生物碱的代谢产生了一组常见的（±）-6,7-二氢-7-羟基-1-羟甲基-5 H-吡咯烷嗪（DHP）衍生负责肿瘤诱导的DNA加合物。体内和体外形成的DHP衍生的DNA加合物的鉴定和定量已由32P后标记/ HPLC方法学。在本文中，我们报道了一个敏感和特异的液相色谱-电喷雾离子化串联质谱（HPLC-ES-MS / MS）的方法来检测形成DHP来源的DNA加合物的发展体外和体内。该方法用于在已知量的同位素标记的DHP-dG和DHP-dA内部标准。HPLC-ES-MS / MS方法准确无误。当将其用于吡咯并立啶生物碱riddelliine和monocrotaline处理的大鼠的肝脏样品中时，该方法提供了有关DNA加合物形成机理的重要新信息。
• An Ammonium Bicarbonate-Enhanced Stable Isotope Dilution UHPLC-MS/MS Method for Sensitive and Accurate Quantification of Acrolein–DNA Adducts in Human Leukocytes
  作者：Ruichuan Yin、Shengquan Liu、Chao Zhao、Meiling Lu、Moon-shong Tang、Hailin Wang

  DOI：10.1021/ac3034695

  日期：2013.3.19

  Acrolein (Acr), a ubiquitous environmental pollutant, can react directly with genomic DNA to form mutagenic adducts without undergoing metabolic activation. To sensitively and accurately quantify Acr–DNA adducts (including structural isomers and stereoisomers) in human leukocytes, we developed an enhanced stable isotope dilution ultrahigh performance liquid chromatography (UHPLC)–tandem mass spectrometry (MS/MS) method using ammonium bicarbonate (NH4HCO3), which is thermally unstable and degrades readily to carbon dioxide and ammonia in heated gas phase. Interestingly, ammonium bicarbonate (as an additive to the mobile phase) not only improves the protonation of AcrdG adducts but also suppresses the formation of MS signal-deteriorating metal–AcrdG complexes during electrospray ionization, leading to the enhancement of their MS detection by 2.3–8.7 times. In contrast, routinely used ammonium salts (ammonium acetate and ammonium formate) and formic acid do not show similar enhancement. The developed method is potentially useful for enhancing ESI-MS detection of other modified 2′-deoxyribonucleosides that have difficulty in protonation and may form excess metal complexes during electrospray ionization. The limits of detection (LODs, S/N = 3) are estimated to be about 40–80 amol. By the use of the developed method, we found that the Acr adducts of three nucleotides (dG, dA, and dC) can be detected in human leukocytes. In addition to the known γ-AcrdG, α-AcrdA is also identified as an Acr-adduct of high abundance (2.5–20 adducts per108 nts).

  丙烯醛（Acrolein，Acr）是一种无处不在的环境污染物，可直接与基因组 DNA 发生反应，形成致突变加合物，而无需经过代谢活化。碳酸氢铵（NH4HCO3）热不稳定，在加热气相中很容易降解为二氧化碳和氨，为了灵敏、准确地定量检测人体白细胞中的 Acr-DNA 加合物（包括结构异构体和立体异构体），我们开发了一种增强型稳定同位素稀释超高效液相色谱（UHPLC）-串联质谱（MS/MS）方法。有趣的是，碳酸氢铵（作为流动相的添加剂）不仅能改善 AcrdG 加合物的质子化，还能抑制电喷雾离子化过程中形成会降低 MS 信号的金属-AcrdG 复合物，从而使其 MS 检测能力提高 2.3-8.7 倍。相比之下，常规使用的铵盐（醋酸铵和甲酸铵）和甲酸则没有类似的增强效果。所开发的方法可用于提高其他修饰的 2′-脱氧核苷酸的 ESI-MS 检测能力，因为这些核苷酸难以质子化，在电喷雾离子化过程中可能会形成过量的金属复合物。检测限（LODs，S/N = 3）估计约为 40-80 amol。通过使用所开发的方法，我们发现可以在人类白细胞中检测到三种核苷酸（dG、dA 和 dC）的 Acr 加合物。除了已知的γ-AcrdG外，α-AcrdA也被鉴定为高丰度的Acr加合物（每108 nts有2.5-20个加合物）。
• Quantification of <i>N</i>²-Carboxymethyl-2′-deoxyguanosine in Calf Thymus DNA and Cultured Human Kidney Epithelial Cells by Capillary High-Performance Liquid Chromatography−Tandem Mass Spectrometry Coupled with Stable Isotope Dilution Method
  作者：Hongxia Wang、Huachuan Cao、Yinsheng Wang

  DOI：10.1021/tx900286c

  日期：2010.1.18

  dilution method and quantified the formation of N2-CMdG in calf thymus DNA and 293T human kidney epithelial cells that were exposed to glyoxal and in calf thymus DNA treated with d-glucose. Our results showed that N2-CMdG was produced at 2−134 lesions per 106 nucleosides in calf thymus DNA when the surrounding glyoxal concentration was increased from 10 to 500 μM and approximately 3−27 lesions per 107 nucleosides

  乙二醛是由葡萄糖的降解和碳水化合物、脂质和 DNA 的 2-脱氧核糖部分的氧化内源产生的。乙二醛也广泛用于工业，存在于香烟烟雾和食品中。乙二醛可以与核碱基和蛋白质结合以产生高级糖基化终产物。N 2 -Carboxymethyl-2'-deoxyguanosine ( N 2 -CMdG) 和环状 1, N 2 -glyoxal-dG 是 DNA 中形成的主要乙二醛加合物。在这项研究中，我们首先评估了这两种加合物的稳定性。原来 1, N 2-glyoxal-dG 非常不稳定，在磷酸盐缓冲盐水中 37°C 孵育 24 小时后，超过 70% 的加合物被分解为 dG。然而，N 2 -CMdG 非常稳定。在相同条件下培养 7 天后，不到 0.5% 的病灶降解为 dG。我们进一步开发了一种灵敏的毛细管液相色谱-电喷雾电离-串联质谱法和稳定同位素稀释方法，并量化了暴露于乙二醛和小牛胸腺中的小牛胸腺 DNA