[13C10,15N5]-dG | 872624-05-0

• 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: [13C10,15N5]-dG
• 英文别名: 2'-Deoxyguanosine-13C10,15N5；2-(15N)azanyl-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxy(113C)methyl)(2,3,4,5-13C4)oxolan-2-yl]-1H-purin-6-one
• CAS: 872624-05-0
• 化学式: C₁₀H₁₃N₅O₄
• 分子量: 282.101
• InChiKey: YKBGVTZYEHREMT-XEJNDJRBSA-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：

  (5-甲酰基呋喃-2-基)甲基硫酸氢酯 、 [13C10,15N5]-dG 反应 24.0h， 生成
  参考文献：
  名称：

  Mutagenicity of 5-Hydroxymethylfurfural in V79 Cells Expressing Human SULT1A1: Identification and Mass Spectrometric Quantification of DNA Adducts Formed

  摘要：

  5-Hydroxymethylfurfural (HMF), a heterocyclic product of the Mallard reaction, is a ubiquitous food contaminant. It has demonstrated hepatocarcinogenic activity in female mice. This effect may originate from sulfo conjugation of the benzylic alcohol yielding 5-sulfooxymethylfurfural (SMF), which is prone to react with DNA via nucleophilic substitution. Indeed, we showed that HMF induces gene mutations in Chinese hamster V79 cells engineered for the expression of human (h) sulfotransferase (SULT)1A1 but not in parental V79 cells. In order to identify potential DNA adducts, we incubated DNA samples with SMF or HMF in aqueous solution. Modified DNA was digested and surveyed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for adducts that may be formed by nucleosides either via nucleophilic substitution at the electrophilic carbon atom of SMF or via imine formation with the aldehyde group present in HMF and SMF. The most abundant adducts formed from SMF, N-6-((2-formylfuran-5-yl)methyl)-2'-deoxyadenosine (N-6-FFM-dAdo) and N-2((2-formylfuran-5-yl)methyl)-2'-deoxyguanosine (N-2-FFM-dGuo), were synthesized, purified, and characterized by H-1 NMR Imine adducts were only detected when DNA was incubated with very high levels of HMF following reduction of the imines to corresponding secondary amines by NaBH3CN. Sensitive techniques based on LC-MS/MS multiple reaction monitoring for the quantification of the adducts in DNA samples were devised using isotope-labeled [N-15(5)]N-6-FFM-dAdo and [C-13(10),N-15(15)]N-2-FFM-dGuo as internal standards. Both 5-methylfurfuryl adducts were detected in DNA from V79-hSULT1A1 treated with HMF but not in DNA from V79 control cells. Considering the lack of other known mutagenic metabolites, we hypothesize that the hepatocarcinogenic potential of HMF originates from the formation of mutagenic SMF.

  DOI：

  10.1021/tx300150n

文献信息

• Regioselective Formation of Acrolein-Derived Cyclic 1,<i>N</i>²-Propanodeoxyguanosine Adducts Mediated by Amino Acids, Proteins, and Cell Lysates
  作者：Fung-Lung Chung、Mona Y Wu、Ahmed Basudan、Marcin Dyba、Raghu G. Nath

  DOI：10.1021/tx3002252

  日期：2012.9.17

  ubiquitous environmental pollutant. It is also formed as a product of lipid peroxidation. Following ring closure via the Michael addition, Acr modifies deoxyguanosine (dG) in DNA by forming cyclic 1,N2-propanodeoxyguanosine adducts (OHPdG). The reactions of Acr with dG yield, depending on the direction of ring closure, two regioisomers, α- and γ-OHPdG, in approximately equal amounts. However, previous 32P-postlabeling

  丙烯醛 (Acr) 是香烟烟雾中的主要成分，是一种普遍存在的环境污染物。它也是脂质过氧化的产物。通过迈克尔加成环闭合后，Acr 通过形成环状 1, N 2 -丙脱氧鸟苷加合物 (OHPdG) 来修饰 DNA 中的脱氧鸟苷 (dG )。Acr 与 dG 的反应产生两种区域异构体，α-和 γ-OHPdG，数量大致相等，这取决于闭环的方向。然而，之前的32 P 标记后研究表明，γ 异构体主要在啮齿动物和人体组织的 DNA 中检测到。由于异构 OHPdG 加合物的潜在差异生物活性，确认和研究 γ 异构体区域选择性形成的化学基础很重要体内。在这项研究中，证实了 γ-OHPdG 加合物确实是体内形成的主要异构体，正如专门为 Acr 衍生的 dG 加合物开发的 LC-MS/MS 方法所证明的那样。此外，我们已经表明，在含氨基化合物（包括氨基酸、蛋白质和细胞裂解物）的存在下，γ-异构体的形成会增加。鉴定出似乎介导