thymidine triphosphate | 365-08-2

• 物质功能分类: 生物化工 - 核苷类药物 - 脱氧核苷酸及其类似物
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: thymidine triphosphate
• 英文别名: thymidine 5'-triphosphate；TTP；thymidine 5'-(tetrahydrogen triphosphate)；Thymidine 5'-triphosphate(4-)；[[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate
• CAS: 365-08-2
• 化学式: C₁₀H₁₃N₂O₁₄P₃
• 分子量: 478.139
• InChiKey: NHVNXKFIZYSCEB-XLPZGREQSA-J

物化性质

• 密度：
  1.922±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5.3
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  250
• 氢给体数：
  2
• 氢受体数：
  14

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• WGK Germany：
  3

制备方法与用途

脱氧胸苷三磷酸是一种脱氧核酸衍生物，可用于有机合成中间体和医药中间体。它主要应用于实验室的有机合成及生物化工研发过程。

反应信息

• 作为反应物：
  描述：

  L-苯丙氨酸甲酯 、 thymidine triphosphate 在 吡啶 、 三甲基氯硅烷 、 氨 作用下， 以 水 为溶剂， 反应 24.0h， 以55%的产率得到
  参考文献：
  名称：

  通过核苷三磷酸与三甲基甲硅烷基氯介导的胺反应，新颖合成核苷5'-磷酸氨基甲酸酯

  摘要：

  在三甲基甲硅烷基氯介导的吡啶中，核苷三磷酸酯（NTPs）与胺的反应以中等收率产生了核苷5'-膦酰胺酸酯，而没有对核苷和氨基酸甲酯的任何预保护。该反应途径与RNA封端反应，DNA或RNA连接反应以及水解酶和核酸酶催化的机制非常相似，涉及在生物系统中形成共价酶-NMP（核苷5'-单磷酸酯）中间体，这可以提供酶促反应的宝贵线索。

  DOI：

  10.1021/jo050716i
• 作为产物：
  描述：

  beta-胸苷 在 磷酸三乙酯 、 2,4,6-三甲基吡啶 、 三氯氧磷 、 三辛胺 、 3C₃₆H₃₀NP₂⁽¹⁺⁾*O₇P₂^(4-) 作用下， 以 乙腈 为溶剂， 反应 22.0h， 以21%的产率得到thymidine triphosphate
  参考文献：
  名称：

  PPN Pyrophosphate: A New Reagent for the Preparation of Nucleoside Triphosphates

  摘要：

  Tris{bis(triphenylphosphoranylidene) ammonium} (PPN) pyrophosphate was accessed via aqueous precipitation and desiccation. The reagent was investigated as a replacement for highly hygroscopic alkylammonium salts in Ludwig-Yoshikawa reactions for the preparation of nucleoside-5 '-triphosphates.

  DOI：

  10.1080/10426507.2014.984032

文献信息

• Lipophilic Triphosphate Prodrugs of Various Nucleoside Analogues
  作者：Xiao Jia、Dominique Schols、Chris Meier

  DOI：10.1021/acs.jmedchem.0c00358

  日期：2020.7.9

  The antiviral efficacy of many nucleoside analogues is strongly dependent on their intracellular activation by host cellular kinases to yield ultimately the bioactive nucleoside analogue triphosphates (NTP). The metabolic conversion of nucleoside analogues into their triphosphates often proceeds insufficiently. We developed a nucleoside triphosphate (NTP) delivery system (the TriPPPro approach), in

  许多核苷类似物的抗病毒功效在很大程度上取决于宿主细胞激酶对它们的胞内活化作用，从而最终产生具有生物活性的核苷类似物三磷酸酯（NTP）。核苷类似物代谢转化为三磷酸酯的过程通常进行得不充分。我们开发了三磷酸核苷（NTP）递送系统（Tri PPPRO法），其中γ-磷酸盐被两个不同的可生物降解的掩蔽单元共价修饰，一个是酰氧基苄基（AB）部分，另一个是烷氧基羰氧基苄基（ACB）基团。这样的化合物通过酶触发的机制在人T淋巴细胞CEM细胞提取物中形成高选择性的NTP，首先失去AB部分，然后失去ACB基团。这使得能够绕过细胞内磷酸化的所有步骤。在此应用此方法将某些中等活性或什至无活性的核苷类似物转化为强大的生物活性代谢物。根据在感染的野生型CD4 +的培养物中针对HIV-1和HIV-2复制的Tri PPP ro-NTP前药的亲脂性，可以获得有效的抗病毒活性。CEM T细胞，更重要的是在缺乏胸苷激酶的CD4
• Gene <i>ytkD</i> of <i>Bacillus subtilis</i> Encodes an Atypical Nucleoside Triphosphatase Member of the Nudix Hydrolase Superfamily
  作者：WenLian Xu、Candice R. Jones、Christopher A. Dunn、Maurice J. Bessman

  DOI：10.1128/jb.186.24.8380-8384.2004

  日期：2004.12.15

  Gene ytkD of Bacillus subtilis , a member of the Nudix hydrolase superfamily, has been cloned and expressed in Escherichia coli . The purified protein has been characterized as a nucleoside triphosphatase active on all of the canonical ribo- and deoxyribonucleoside triphosphates. Whereas all other nucleoside triphosphatase members of the superfamily release inorganic pyrophosphate and the cognate nucleoside monophosphate, YtkD hydrolyses nucleoside triphosphates in a stepwise fashion through the diphosphate to the monophosphate, releasing two molecules of inorganic orthophosphate. Contrary to a previous report, our enzymological and genetic studies indicate that ytkD is not an orthologue of E. coli mutT .

  摘要 基因 ytkD 的 基因 ytkD 是 Nudix水解酶超家族的成员，已被克隆并在 大肠杆菌 .纯化后的蛋白质被鉴定为一种核苷三磷酸酶，对所有典型的核糖核苷和脱氧核糖核苷三磷酸酶都有活性。该超家族的所有其他核苷三磷酸酶成员都会释放出无机焦磷酸和同源的核苷单磷酸，而 YtkD 则以逐步的方式从二磷酸水解到单磷酸，释放出两分子无机正磷酸盐。与之前的报告相反，我们的酶学和遗传学研究表明 ytkD 不是 大肠杆菌 mutT .
• MazG, a Nucleoside Triphosphate Pyrophosphohydrolase, Interacts with Era, an Essential GTPase in<i>Escherichia coli</i>
  作者：Junjie Zhang、Masayori Inouye

  DOI：10.1128/jb.184.19.5323-5329.2002

  日期：2002.10

  Era is an essential GTPase inEscherichia coli, and Era has been implicated in a number of cellular functions. Homologues of Era have been identified in various bacteria and some eukaryotes. Using theeragene as bait in the yeast two-hybrid system to screenE. coligenomic libraries, we discovered that Era interacts with MazG, a protein of unknown function which is highly conserved among bacteria. The direct interaction between Era and MazG was also confirmed in vitro, being stronger in the presence of GDP than in the presence of GTPγS. MazG was characterized as a nucleoside triphosphate pyrophosphohydrolase which can hydrolyze all eight of the canonical ribo- and deoxynucleoside triphosphates to their respective monophosphates and PP_i, with a preference for deoxynucleotides. AmazGdeletion strain ofE. coliwas constructed by replacing themazGgene with a kanamycin resistance gene. UnlikemutT, a gene for another conserved nucleotide triphosphate pyrophosphohydrolase that functions as a mutator gene, themazGdeletion did not result in a mutator phenotype inE. coli.

  摘要Era 是大肠杆菌（Escherichia coli）中一种重要的 GTP 酶，Era 与多种细胞功能有关。目前已在多种细菌和一些真核生物中发现了 Era 的同源物。我们利用酵母双杂交系统中的 Eeragene 作为诱饵筛选大肠杆菌基因组文库，发现 Era 与 MazG 相互作用，MazG 是一种功能未知的蛋白质，在细菌中高度保守。我们还在体外证实了 Era 与 MazG 之间的直接相互作用，这种作用在 GDP 存在时比在 GTPγS 存在时更强。MazG 被鉴定为一种核苷三磷酸焦磷酸水解酶，可将所有八种核糖核苷和脱氧核苷三磷酸水解为各自的单磷酸和 PPi，并偏好脱氧核苷酸。通过用卡那霉素抗性基因替换 AmazG 基因，构建了大肠杆菌 AmazG 基因缺失株。与作为突变基因的另一种保守的核苷酸三磷酸焦磷酸水解酶基因mutT不同，AmazG缺失并没有导致大肠杆菌出现突变表型。
• Saccharomyces cerevisiae nucleoside-diphosphate kinase: Purification, characterization, and substrate specificity
  作者：Ambrose Y. Jong、Jin.J. Ma

  DOI：10.1016/0003-9861(91)90129-7

  日期：1991.12

  Nucleoside-diphosphate kinase is an enzyme which catalyzes the phosphorylation of nucleoside diphosphates into the corresponding triphosphates for nucleic acid biosynthesis. In this communication, we describe the purification and characterization of nucleoside-diphosphate kinase from yeast. The purified protein appears to be homogeneous by sodium dodecyl sulfate-polyacrylamide gel analysis, with a

  核苷二磷酸激酶是一种酶，可将核苷二磷酸磷酸化为相应的三磷酸以进行核酸生物合成。在本交流中，我们描述了酵母中核苷二磷酸激酶的纯化和表征。通过十二烷基硫酸钠-聚丙烯酰胺凝胶分析，纯化的蛋白质似乎是均质的，分子量约为17,000-18,000。快速蛋白质液相色谱Superose 12凝胶过滤的估算结果表明，其天然分子量约为68,000至70,000。结果表明，酵母核苷二磷酸激酶由四个亚基组成。底物特异性研究表明，核苷二磷酸酯（NDP）作为磷酸盐受体的相对活性为dTDP大于CDP大于UDP大于dUDP大于GDP大于或等于dGDP大于dCDP大于dADP大于ADP ; 三磷酸供体的相对活性的顺序为：UTP大于dTTP大于CTP大于dCTP大于dATP大于ATP大于或等于dGTP大于GTP。已确定dTDP，dGDP，dCDP，dUDP，CDP和UDP的Km和Vm。速率常数研究表明，纯化的NDP激酶在较小程度上更喜欢使用dTDP（约800
• Genetic analysis of the dTDP-rhamnose biosynthesis region of the Escherichia coli VW187 (O7:K1) rfb gene cluster: identification of functional homologs of rfbB and rfbA in the rff cluster and correct location of the rffE gene
  作者：C L Marolda、M A Valvano

  DOI：10.1128/jb.177.19.5539-5546.1995

  日期：1995.10

  The O-repeating unit of the Escherichia coli O7-specific lipopolysaccharide is made of galactose, mannose, rhamnose, 4-acetamido-4,6-dideoxyglucose, and N-acetyglucosamine. We have recently characterized the genes involved in the biosynthesis of the sugar precursor GDP-mannose occurring in the E. coli O7:K1 strain VW187 (C. L. Marolda and M. A. Valvano, J. Bacteriol. 175:148-158, 1993). In the present study, we identified and sequenced the rfbBDAC genes encoding the enzymes for the biosynthesis of another precursor, dTDP-rhamnose. These genes are localized on the upstream end of the rfbEcO7 region, and they are strongly conserved compared with similar genes found in various enteric and nonenteric bacteria. Upstream of rfbB we identified a DNA segment containing the rfb promoter and a highly conserved untranslated leader sequence also present in the promoter regions of other surface polysaccharide gene clusters. Also, we have determined that rfbB and rfbA have homologs, rffG (o355) and rffH (o292), respectively, located on the rff cluster, which is involved in the synthesis of enterobacterial common antigen. We provide biochemical evidence that rffG and rffH encode dTDP-glucose dehydratase and glucose-1-phosphate thymidylyltransferase activities, respectively, and we also show that rffG complemented the rfbB defect in the O7+ cosmid pJHCV32. We also demonstrate that rffG is distinct from rffE and map the rffE gene to the second gene of the rff cluster.

  大肠杆菌O7专属脂多糖的O-重复单元由半乳糖、甘露糖、鼠李糖、4-乙酰胺基-4,6-二脱氧葡萄糖和N-乙酰葡萄糖胺组成。我们最近鉴定了参与E. coli O7:K1菌株VW187中GDP-甘露糖前体生物合成的基因（C.L. Marolda和M.A. Valvano，J. Bacteriol. 175:148-158，1993）。在本研究中，我们确定并测序了rfbBDAC基因，这些基因编码另一种前体dTDP-鼠李糖的生物合成酶。这些基因位于rfbEcO7区域的上游端，与在各种肠道和非肠道细菌中发现的类似基因相比，它们具有很强的保守性。在rfbB的上游，我们确定了一个DNA片段，其中包含rfb启动子和高度保守的未翻译的领导序列，这些序列也存在于其他表面多糖基因簇的启动子区域中。此外，我们确定了rfbB和rfbA的同源基因rfFG（o355）和rfFH（o292），它们分别位于rfF群集中，参与肠道细菌共同抗原的合成。我们提供了生化证据表明rfFG和rfFH分别编码dTDP-葡萄糖脱水酶和葡萄糖-1-磷酸己糖基转移酶活性，并且我们还展示了rfFG在O7 + cosmid pJHCV32中补充了rfbB缺陷。我们还证明了rfFG与rfFE不同，并将rfFE基因定位于rfF群集的第二个基因。