2'-脱氧胞苷三磷酸 | 2056-98-6

• 物质功能分类: 生物化工 - 核苷类药物 - 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
• 中文名称: 2'-脱氧胞苷三磷酸
• 英文名称: 2'-deoxycytidine 5'-triphosphate
• 英文别名: dCTP；deoxycytidine triphosphate；2’-deoxycytidine-5’-triphosphate；2'-deoxycytidine triphosphate；2′-deoxycytidine 5′-triphosphate；2'-Deoxycytidine-5'-triphosphate；[[(2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
• CAS: 2056-98-6
• 化学式: C₉H₁₆N₃O₁₃P₃
• 分子量: 467.16
• InChiKey: RGWHQCVHVJXOKC-SHYZEUOFSA-N

物化性质

• 沸点：
  811.5±75.0 °C(Predicted)
• 密度：
  2.38±0.1 g/cm3(Predicted)
• 物理描述：
  Solid
• 碰撞截面：
  184.9 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  -5.6
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  248
• 氢给体数：
  6
• 氢受体数：
  13

安全信息

• 储存条件：
  | 存储温度 | 2-8℃ |

制备方法与用途

生物活性

脱氧胞苷三磷酸（dCTP）是用于DNA合成的核苷三磷酸，也可用于实时PCR、cDNA合成和DNA测序等研究。

人类内源性代谢物

体外研究

对来自小鼠淋巴瘤、多发性骨髓瘤、髓样肿瘤及嗜酸性粒细胞增多症（mastocytoma）的13种细胞系进行抗增殖作用敏感性检测，发现它们之间的敏感度差异高达100倍。研究还发现了这些细胞对2′-脱氧胞苷-5′-三磷酸盐（dCTP）含量与抗增殖敏感性的反向相关性，并推测在细胞暴露于阿糖胞苷（ara-C）期间降低dCTP含量可能提高细胞的敏感度。

脱氧胞苷三磷酸三钠盐是磷脂乙醇胺胞苷基转移酶的底物。

反应信息

• 作为反应物：
  描述：

  2'-脱氧胞苷三磷酸 在 deoxyribonucleoside triphosphate triphosphohydrolase 、 sodium chloride 、 magnesium chloride 、 bovine serum albumin 作用下， 以 甘油 为溶剂， 生成 2'-脱氧胞嘧啶核苷
  参考文献：
  名称：

  Mechanisms of Allosteric Activation and Inhibition of the Deoxyribonucleoside Triphosphate Triphosphohydrolase from Enterococcus faecalis

  摘要：

  Background: EF1143 from Enterococcus faecalis is a deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase. Results: Enzymatic studies and crystal structure of EF1143 bound to dNTPs show that dNTP binding at two adjacent allosteric sites can differentially modulate enzyme catalysis. Conclusion: EF1143 enzyme catalysis is differentially regulated by four dNTPs. Significance: Learning how the enzyme activity is regulated by substrates is fundamental for understanding enzyme catalysis and allostery.EF1143 from Enterococcus faecalis, a life-threatening pathogen that is resistant to common antibiotics, is a homo-tetrameric deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase (dNTPase), converting dNTPs into the deoxyribonucleosides and triphosphate. The dNTPase activity of EF1143 is regulated by canonical dNTPs, which simultaneously act as substrates and activity modulators. Previous crystal structures of apo-EF1143 and the protein bound to both dGTP and dATP suggested allosteric regulation of its enzymatic activity by dGTP binding at four identical allosteric sites. However, whether and how other canonical dNTPs regulate the enzyme activity was not defined. Here, we present the crystal structure of EF1143 in complex with dGTP and dTTP. The new structure reveals that the tetrameric EF1143 contains four additional secondary allosteric sites adjacent to the previously identified dGTP-binding primary regulatory sites. Structural and enzyme kinetic studies indicate that dGTP binding to the first allosteric site, with nanomolar affinity, is a prerequisite for substrate docking and hydrolysis. Then, the presence of a particular dNTP in the second site either enhances or inhibits the dNTPase activity of EF1143. Our results provide the first mechanistic insight into dNTP-mediated regulation of dNTPase activity.

  DOI：

  10.1074/jbc.m113.524207
• 作为产物：
  描述：

  2'-脱氧胞嘧啶核苷 在 吡啶 、 水 、 碘 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.75h， 生成 2'-脱氧胞苷三磷酸
  参考文献：
  名称：

  一种核苷四磷酸的合成方法

  摘要：

  本发明公开了一种核苷四磷酸的合成方法。所述方法包括以下步骤：将核苷与环状磷酸化试剂发生选择性磷酸化反应，再经氧化、水解开环，即得所述核苷四磷酸。所述环状磷酸化试剂的结构如式I所示：式I。本方法将核苷在该高选择性磷酸化试剂作用下,选择性地生成5＇‑核苷四磷酸，在此过程中并不需要将3＇‑OH(以及2＇‑OH)保护起来，即能有效抑制3＇(以及2＇‑)四磷酸的生成。本发明合成的核苷四磷酸在DNA测序、标记、延伸等生物学领域具有广泛用途，目前其销售价格昂贵，合成方法复杂，反应选择性差；而本发明提供的合成方法选择性好，容易分离纯化，且所需实验条件简单，合成过程均为常规化学反应，可用于大规模推广使用。

  公开号：

  CN109232693A
• 作为试剂：
  描述：

  beta-胸苷 在 recombinant Cryptosporidium parvum thymidine kinase 、 2'-脱氧胞苷三磷酸 、 5’-三磷酸腺苷 作用下， 生成 胸苷酸
  参考文献：
  名称：

  Prodrug Activation by Cryptosporidium Thymidine Kinase

  摘要：

  Cryptosporidium spp. cause acute gastrointestinal disease that can be fatal for immunocompromised individuals. These protozoan parasites are resistant to conventional antiparasitic chemotherapies and the currently available drugs to treat these infections are largely ineffective. Genomic studies suggest that, unlike other protozoan parasites, Cryptosporidium is incapable of de novo pyrimidine biosynthesis. Curiously, these parasites possess redundant pathways to produce dTMP, one involving thymidine kinase (TK) and the second via thymidylate synthase-dihydrofolate reductase. Here we report the expression and characterization of TK from C. parvum. Unlike other TKs, CpTK is a stable trimer in the presence and absence of substrates and the activator dCTP. Whereas the values of k(cat) = 0.28 s(-1) and K(m)(,ATP) = 140 microm are similar to those of human TK1, the value of K(m)(thymidine) = 48 microm is 100-fold greater, reflecting the abundance of thymidine in the gastrointestinal tract. Surprisingly, the antiparasitic nucleosides AraT, AraC, and IDC are not substrates for CpTK, indicating that Cryptosporidium possesses another deoxynucleoside kinase. Trifluoromethyl thymidine and 5-fluorodeoxyuridine are good substrates for CpTK, and both compounds inhibit parasite growth in an in vitro model of C. parvum infection. Trifluorothymidine is also effective in a mouse model of acute disease. These observations suggest that CpTK-activated pro-drugs may be an effective strategy for treating cryptosporidiosis.

  DOI：

  10.1074/jbc.m110.101543

文献信息

• [EN] ELECTROCHEMICALLY-CLEAVABLE LINKERS<br/>[FR] LIEURS CLIVABLES PAR VOIE ÉLECTROCHIMIQUE
  申请人：MICROSOFT TECHNOLOGY LICENSING LLC

  公开号：WO2021158412A1

  公开（公告）日：2021-08-12

  This disclosure provides electrochemically-cleavable linkers with cleavage potentials that are less than the redox potential of the solvent in which the linkers are used. In some applications, the solvent may be water or an aqueous buffer solution. The linkers may be used to link a nucleotide to a bound group. The linkers include a cleavable group which may be one of a methoxybenzyl alcohol, an ester, a propargyl thioether, or a trichloroethyl ether. The linkers may be cleaved in solvent by generating an electrode potential that is less than the redox potential of the solvent. In some implementations, an electrode array may be used to generate localized electrode potentials which selectively cleave linkers bound to the activated electrode. Uses for the linkers include attachment of blocking groups to nucleotides in enzymatic oligonucleotide synthesis.

  这份披露提供了具有低于使用的溶剂的氧化还原电位的可电化学裂解连接物。在某些应用中，溶剂可能是水或水溶液缓冲液。这些连接物可用于将核苷酸连接到结合基团。连接物包括可裂解基团，可能是甲氧基苯甲醇、酯、丙炔硫醚或三氯乙基醚中的一种。通过产生低于溶剂的氧化还原电位的电极电位，可以在溶剂中裂解这些连接物。在某些实施中，可以使用电极阵列来产生局部电极电位，从而选择性地裂解与激活电极结合的连接物。这些连接物的用途包括在酶催化寡核苷酸合成中将阻断基团附着到核苷酸上。
• [EN] NOVEL MODULATORS OF CELL CYCLE CHECKPOINTS AND THEIR USE IN COMBINATION WITH CHECKPOINT KINASE INHIBITORS<br/>[FR] NOUVEAUX MODULATEURS DE POINTS DE CONTRÔLE DU CYCLE CELLULAIRE ET LEUR UTILISATION EN COMBINAISON AVEC DES INHIBITEURS DE KINASE DE POINT DE CONTRÔLE
  申请人：SCHERING CORP

  公开号：WO2009061781A1

  公开（公告）日：2009-05-14

  In its many embodiments, the present invention provides a novel class of pyrimidine analogs of formula (V) as targeted mechanism-based modulators of cell cycle checkpoints. Cancers and/or malignancies can be treated by administration of a cell cycle checkpoint modulator of the invention. Also discussed are suitable combinations of the cell cycle checkpoint modulator with a checkpoint kinase inhibitor to produce synergistic apoptosis in cancer cells. The invention includes methods of treating cancers by administering the combination of the cell cycle checkpoint modulator and the checkpoint kinase inhibitor, pharmaceutical compositions comprising the activator as well as the combination and pharmaceutical kits.

  在其多种实施方式中，本发明提供了一类新型的嘧啶类似物，其化学式为（V），作为细胞周期检查点的靶向机制调节剂。可以通过给予本发明的细胞周期检查点调节剂来治疗癌症和/或恶性肿瘤。还讨论了适当的细胞周期检查点调节剂与检查点激酶抑制剂的组合，以在癌细胞中产生协同凋亡。该发明包括通过给予细胞周期检查点调节剂和检查点激酶抑制剂的组合来治疗癌症的方法，以及包含激活剂以及该组合的药物组合和药物配套工具。
• [EN] COMPOSITIONS AND METHODS FOR SYNTHESIS OF PHOSPHORYLATED MOLECULES<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE SYNTHÈSE DE MOLÉCULES PHOSPHORYLÉES
  申请人：UNIV CALIFORNIA

  公开号：WO2019195494A1

  公开（公告）日：2019-10-10

  The invention provides compositions and methods for synthesis of phosphorylated organic compounds, including nucleoside triphosphates.

  这项发明提供了合成磷酸化有机化合物的组合物和方法，包括核苷三磷酸。
• [EN] DIASTEREOSELECTIVE SYNTHESIS OF PHOSPHATE DERIVATIVES AND OF THE GEMCITABINE PRODRUG NUC-1031<br/>[FR] SYNTHÈSE DIASTÉRÉOSÉLECTIVE DE DÉRIVÉS DE PHOSPHATE ET DU PROMÉDICAMENT DE GEMCITABINE NUC-1031
  申请人：NUCANA BIOMED LTD

  公开号：WO2017098252A1

  公开（公告）日：2017-06-15

  The present invention provides a method for the preparation of intermediates useful in the synthesis of gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate. It also provides a method of preparing gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate.

  本发明提供了一种用于合成吉西他滨-[苯基苯氧基-L-丙氨酰)]-磷酸盐中间体的制备方法。它还提供了一种制备吉西他滨-[苯基苯氧基-L-丙氨酰)]-磷酸盐的方法。
• Dosing regimen for gemcitabine HCV therapy
  申请人：——

  公开号：US20030225029A1

  公开（公告）日：2003-12-04

  A dosage regiment for the treatment of a Flaviviridae infection, including a hepatitis C viral infection, that includes administering gemcitabine (or its salt, prodrug or derivative, as described herein) in a dosage range of approximately 50 mg/m 2 to about 1300 mg/m 2 per day for between one and seven days (e.g. 1, 2, 3, 4, 5, 6, or 7 days) followed by cessation of therapy. Viral load is optionally monitored over time, and after cessation, viral rebound is monitored. Therapy is not resumed unless a significant viral load is again observed, and then therapy for 1-7 days and more preferred, 1, 2 or 3 days, is repeated. This therapy can be continued indefinitely to monitor and maintain the health of the patient.

  一种用于治疗黄病毒科感染的剂量方案，包括丙型肝炎病毒感染，在一到七天内每天给予吉西他滨（或其盐、前药或衍生物，如本文所述）的剂量范围约为50毫克/平方米至约1300毫克/平方米，随后停止治疗。可选择随时间监测病毒载量，并在停止治疗后监测病毒反弹。除非再次观察到显著的病毒载量，否则不会恢复治疗，然后重复1-7天的治疗，更倾向于1、2或3天。这种疗法可以无限期地继续以监测和维护患者的健康。