thymidylyl-(3'-5')-2'-deoxyguanosine | 4251-20-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （3'->5'）-二核苷酸和类似物
• 英文名称: thymidylyl-(3'-5')-2'-deoxyguanosine
• 英文别名: [(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methyl [(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] hydrogen phosphate
• CAS: 4251-20-1
• 化学式: C₂₀H₂₆N₇O₁₁P
• 分子量: 571.44
• InChiKey: LEPRUDHQLYFMNB-PRSXHHODSA-N

物化性质

• 密度：
  2.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  249
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  thymidylyl-(3'-5')-2'-deoxyguanosine 在 二苯甲酮 、 氧气 作用下， 以 水 为溶剂， 反应 1.0h， 生成 d(TpL)
  参考文献：
  名称：

  Buchko, Garry W.; Cadet, Jean, Canadian Journal of Chemistry, 1992, vol. 70, # 6, p. 1827 - 1832

  摘要：

  DOI：
• 作为产物：
  描述：

  Phosphoric acid (2R,3S,5R)-5-(2-amino-6-oxo-1,6-dihydro-purin-9-yl)-3-hydroxy-tetrahydro-furan-2-ylmethyl ester (2R,3S,5R)-5-(2,4-dioxo-5-phenylsulfanylmethyl-3,4-dihydro-2H-pyrimidin-1-yl)-2-hydroxymethyl-tetrahydro-furan-3-yl ester 在 水 作用下， 生成 thymidylyl-(3'-5')-2'-deoxyguanosine
  参考文献：
  名称：

  含有5-（苯硫甲基）-2'-脱氧尿苷：5-（2'-脱氧尿苷基）甲基自由基的特定光不稳定前体的寡聚脱氧核苷酸的合成和紫外光解。

  摘要：

  标题外环基（2）是通过光化学裂解5-（苯硫基甲基）-2'-脱氧尿苷（8）而产生的。后者的硫代核苷（8）通过使用亚磷酰胺化学方法自动进行DNA合成成功地掺入了DNA寡聚物中。在有氧条件下，含有8个寡核苷酸的紫外线暴露会引起特定的基础病变。在详细的NMR和质谱分析的基础上，已分离并进一步表征了光产物。

  DOI：

  10.1021/ol005643y

文献信息

• Identification of the α and β Anomers of 1-(2-Deoxy-d-Erythro-Pentofuranosyl)-Oxaluric Acid at the Site of Riboflavin-mediated Photooxidation of Guanine in 2′-Deoxyguanosine and Thymidylyl-(3′-5′)-2′-Deoxyguanosine†
  作者：Garry W. Buchko、Jean Cadet

  DOI：10.1562/2005-06-01-ra-562

  日期：——

  spectroscopy, fast atom bombardment mass spectrometry, and enzymatic analyses. Both alpha-dOx and Tpalpha-dOx slowly convert back into the modified beta-deoxyribonucleoside, indicating that the furanosidic anomers are in dynamic equilibrium. Relative to TpdG, the rate of hydrolysis of Tpbeta-dOx and Tpalpha-dOx by spleen phosphodiesterase is greatly reduced. Hot piperidine (1.0 M, 90 degrees C, 30 min) destroys

  氧饱和水溶液中350nm的光经核黄素介导的2'-脱氧鸟苷（dG）和胸苷基-（3'-5'）-2'-脱氧鸟苷（TpdG）的光敏作用的产物已鉴定为1 -（2-脱氧-β-D-异戊-呋喃糖基）草酸（β-dOx）和胸苷基-（3'-5'）-1-（2-脱氧-β-D-异戊-呋喃糖基）草酸（ Tpbeta-dOx）。在水溶液中，修饰的β-脱氧核糖核苷缓慢转化为α-端基异构体，生成α-dOx和Tpalpha-dOx。这些修饰的核苷和二核苷单磷酸酯已通过HPLC分离，并通过质子和碳NMR光谱，快速原子轰击质谱和酶促分析进行了表征。α-dOx和Tpalpha-dOx都缓慢地转化回修饰的β-脱氧核糖核苷，表明呋喃硅前体处于动态平衡状态。相对于TpdG，脾磷酸二酯酶水解Tpbeta-dOx和Tpalpha-dOx的速率大大降低。热哌啶（1.0 M，90摄氏度，30分钟）会破坏Tpbeta-dOx和Tpalpha-dOx
• Alkylation of anionic DNA bases by styrene 7,8-oxide
  作者：Mikko Koskinen、Elke K. H. Schweda、Kari Hemminki

  DOI：10.1039/a906658f

  日期：——

  Styrene 7,8-oxide (SO), a reactive epoxide that has been classified as a probable human carcinogen, was allowed to react under alkaline conditions with 2′-deoxyguanosine and thymidine monophosphates as well as with the dinucleotide dGpdT. The reaction products were separated by high-performance liquid chromatography and were characterised by UV and electrospray mass spectroscopy, the latter showing the ability to differentiate the isomerism of the hydroxyphenylethyl moiety of the adduct. The main alkylation products of the deoxyguanosine monophosphates at high pH were those reacted at the 1- (through the β-carbon of the epoxide), N2- (α-carbon) and 7-positions (β- and α-carbons) of guanine followed by alkylation of the phosphate group. The formation of a novel diastereomeric pair of N 2-guanine adducts connected to the β-carbon of SO was identified and characterised. Furthermore, two different geometrical isomers of 1-guanine were detected. For thymidine nucleotide, base alkylation under neutral conditions was almost negligible, but at pH 10.5, alkylation at the 3-position was very prominent. The same base-adducts and the pH-effects were observed in the case of dGpdT alkylation. However, no phosphate alkylation was detected in the case of the dinucleotide.

  苯乙烯 7,8-氧化物（SO）是一种活性环氧化物，已被归类为可能的人类致癌物，它可在碱性条件下与 2′-脱氧鸟苷和胸苷单磷酸盐以及二核苷酸 dGpdT 发生反应。反应产物通过高效液相色谱法分离，并通过紫外光谱和电喷雾质谱进行表征，后者显示了区分加合物中羟基苯乙基分子异构体的能力。在高 pH 值条件下，脱氧鸟苷单磷酸酯的主要烷基化产物是鸟嘌呤的 1-位（通过环氧化物的 β-碳）、N2-位（α-碳）和 7-位（β-和 α-碳）发生反应，然后磷酸基发生烷基化。结果发现并表征了与 SO 的 β 碳相连的 N 2-鸟嘌呤加合物形成的一对新型非对映异构体。此外，还检测到了 1-鸟嘌呤的两种不同几何异构体。胸苷核苷酸在中性条件下的碱基烷基化几乎可以忽略不计，但在 pH 值为 10.5 时，3 位的烷基化非常明显。在 dGpdT 烷基化的情况下，也观察到了同样的碱基加成和 pH 值效应。不过，在二核苷酸中没有检测到磷酸烷基化。
• DNA Tandem Lesions Containing 8-Oxo-7,8-dihydroguanine and Formamido Residues Arise from Intramolecular Addition of Thymine Peroxyl Radical to Guanine
  作者：Thierry Douki、Johann Rivière、Jean Cadet

  DOI：10.1021/tx0155909

  日期：2002.3.1

  monophosphates (dGpdT and dTpdG). First, the peroxyl radical-induced degradation of guanine within dGpdT and dTpdG was studied in order to assess the possibility of intramolecular electron transfer between guanine and thymine peroxyl radicals. Then, the formation of a series of tandem lesions involving a formamido residue, thymine glycols, 8-oxodG, and oxazolone was monitored within aerated aqueous solutions

  带有嘧啶碱基和鸟嘌呤残基的二磷酸核苷单磷酸盐的充气水溶液暴露于电离辐射会导致形成8-oxo-7,8-dihydroguanine / formamido串联损伤（8-oxodG / dF）。在分离的DNA内形成后者损伤的最新证据强调了这类损伤的可能生物学相关性。因此，对含胸腺嘧啶和鸟嘌呤的二磷酸核苷单磷酸酯（dGpdT和dTpdG）进行了8-oxodG / dF形成的广泛机理研究。首先，研究过氧自由基在dGpdT和dTpdG中诱导鸟嘌呤的降解，以评估鸟嘌呤和胸腺嘧啶过氧自由基之间分子内电子转移的可能性。然后，形成一系列涉及甲酰胺残基，胸腺嘧啶二醇的串联损伤，在暴露于伽玛射线的dTpdG和dGpdT充气水溶液中监测8-oxodG和oxazolone。除了以高产率形成除8-oxodG / dF以外的串联损伤，导致我们提出了一种新的机制，该机制涉及在鸟嘌呤部分添加胸腺嘧啶过氧自由基。这得到（18）O标记实验的支持。
• A Novel Vicinal Lesion Obtained from the Oxidative Photosensitization of TpdG:  Characterization and Mechanistic Aspects
  作者：Thierry Delatour、Thierry Douki、Didier Gasparutto、Marie-Christine Brochier、Jean Cadet

  DOI：10.1021/tx980066w

  日期：1998.9.1

  riboflavin associated with isotopic labeling experiments using enriched oxygen and water provided relevant information on the mechanism of formation of the adduct. The results of these experiments clearly demonstrated that the initial event leading to the formation of the lesion is the abstraction of a hydrogen atom from the methyl group of the thymine base moiety of TpdG. This is followed by the addition

  从充气水溶液中TpdG的光敏作用中分离出一种新型的邻位基础病变。一维和二维NMR测量与质谱一起使用可准确表征新加合物。胍的化学检测在3'-OH末端的碱基部分提供了其他结构信息。总之，实验结果表明在5'-OH末端的嘧啶环和在3'-OH末端的咪唑环之间通过亚甲基桥存在共价键。TbdG，胸苷和2'-脱氧鸟苷在二苯甲酮，甲萘醌，核黄素或核黄素与使用富氧和水的同位素标记实验相关联，提供了有关加合物形成机理的相关信息。这些实验的结果清楚地表明，导致病变形成的初始事件是从TpdG的胸腺嘧啶碱基部分的甲基中提取出氢原子。随后在鸟嘌呤环的C-4原子上添加以甲基为中心的基团，在与分子氧反应并随后发生重排后会引起邻位病变。
• Electron transfer in di(deoxy)nucleoside phosphates in aqueous solution: rapid migration of oxidative damage (via adenine) to guanine
  作者：Luis Pedro Candeias、Steen Steenken

  DOI：10.1021/ja00059a044

  日期：1993.3

  In aqueous solution, the one-electron loss centers created statistically by the oxidant SO4.- or by photoionization in di(2'-deoxy)nucleoside phosphates (DNPs) containing the base guanine (G) become localized at G, as concluded from pulse radiolysis and 193-nm laser photolysis experiments. From the latter it is evident that, in the case of adenylyl(3'-->5')guanosine (ApG), the charge-transfer process is complete in less-than-or-equal-to 50 ns. With DNPs containing a pyrimidine and the purine base adenine, the oxidative damage is collected by the adenine moiety (k greater-than-or-equal-to 2 X 10(5) s-1).