2-硫代尿苷酸 | 29123-25-9

• 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-硫代尿苷酸
• 英文名称: ((2R,3S,4R,5R)-3,4-dihydroxy-5-(4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl phosphate
• 英文别名: 2-thio-[5']uridylic acid；2-Thio-[5']uridylsaeure；2'-Thiouridin-5'-phosphat；2-Thio-uridin-5'-phosphat；2-Thio-UMP；[(2R,3S,4R,5R)-3,4-dihydroxy-5-(4-oxo-2-sulfanylidenepyrimidin-1-yl)oxolan-2-yl]methyl dihydrogen phosphate
• CAS: 29123-25-9
• 化学式: C₉H₁₃N₂O₈PS
• 分子量: 340.251
• InChiKey: OEUXFECIJDETRF-XVFCMESISA-N

物化性质

• 密度：
  1.88±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  181
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  α-D-glucose-1-monophosphate bistributylammonium salt 、 2-硫代尿苷酸 生成 MRS2690
  参考文献：
  名称：

  尿苷5'-二磷酸葡萄糖类似物作为人P2Y14受体激动剂的结构-活性关系。

  摘要：

  UDP葡萄糖（UDPG）及其衍生物是Gi蛋白偶联的P2Y14受体的天然激动剂，它存在于免疫系统中。我们合成并表征了在碱基，核糖和葡萄糖部分修饰的UDPG的药理学新类似物，作为结合建模设计新配体的基础。通过工程化的Galpha-q / i蛋白将在COS-7细胞中表达的重组人P2Y14受体与磷脂酶C偶联。尿嘧啶或核糖部分的大多数修饰废除了活性。这是最不被允许的P2Y受体之一。然而，在15（EC50 49 +/- 2 nM）中的2-硫尿嘧啶修饰将UDPG（而不是UDP-葡萄糖醛酸）的效力提高了7倍。4-硫代类似物13与UDPG等价，但是S-烷基化是有害的。化合物15停靠在基于罗丹蛋白的受体同源性模型中，该模型正确预测了UDP-果糖，UDP-甘露糖和UDP-肌醇的有效激动作用。UDPG的己糖部分与多个H键和带电荷的残基相互作用，并为激动剂修饰提供了肥沃的区域。

  DOI：

  10.1021/jm061222w
• 作为产物：
  描述：

  2-硫代尿苷 在 磷酸三甲酯 、 Proton Sponge 、 三氯氧磷 作用下， 反应 2.0h， 生成 2-硫代尿苷酸
  参考文献：
  名称：

  尿苷5'-二磷酸葡萄糖类似物作为人P2Y14受体激动剂的结构-活性关系。

  摘要：

  UDP葡萄糖（UDPG）及其衍生物是Gi蛋白偶联的P2Y14受体的天然激动剂，它存在于免疫系统中。我们合成并表征了在碱基，核糖和葡萄糖部分修饰的UDPG的药理学新类似物，作为结合建模设计新配体的基础。通过工程化的Galpha-q / i蛋白将在COS-7细胞中表达的重组人P2Y14受体与磷脂酶C偶联。尿嘧啶或核糖部分的大多数修饰废除了活性。这是最不被允许的P2Y受体之一。然而，在15（EC50 49 +/- 2 nM）中的2-硫尿嘧啶修饰将UDPG（而不是UDP-葡萄糖醛酸）的效力提高了7倍。4-硫代类似物13与UDPG等价，但是S-烷基化是有害的。化合物15停靠在基于罗丹蛋白的受体同源性模型中，该模型正确预测了UDP-果糖，UDP-甘露糖和UDP-肌醇的有效激动作用。UDPG的己糖部分与多个H键和带电荷的残基相互作用，并为激动剂修饰提供了肥沃的区域。

  DOI：

  10.1021/jm061222w

文献信息

• Human P2Y₁₄ Receptor Agonists: Truncation of the Hexose Moiety of Uridine-5′-Diphosphoglucose and Its Replacement with Alkyl and Aryl Groups
  作者：Arijit Das、Hyojin Ko、Lauren E. Burianek、Matthew O. Barrett、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1021/jm901432g

  日期：2010.1.14

  Uridine-5′-diphosphoglucose (UDPG) activates the P2Y14 receptor, a neuroimmune system GPCR. P2Y14 receptor tolerates glucose substitution with small alkyl or aryl groups or its truncation to uridine 5′-diphosphate (UDP), a full agonist at the human P2Y14 receptor expressed in HEK-293 cells. 2-Thiouracil derivatives displayed selectivity for activation of the human P2Y14 vs the P2Y6 receptor, such as

  尿苷-5'-二磷酸葡萄糖 (UDPG) 激活 P2Y 14受体，这是一种神经免疫系统 GPCR。P2Y 14受体耐受用小烷基或芳基取代的葡萄糖或其截断为尿苷 5'-二磷酸 (UDP)，这是在 HEK-293 细胞中表达的人类 P2Y 14受体的完全激动剂。2-硫尿嘧啶衍生物显示出激活人 P2Y 14与 P2Y 6受体的选择性，例如 2-硫代-UDP 4（EC 50 = 1.92 nM，P2Y 14，选择性比 P2Y 6 高224 倍）及其β-丙氧基酯18 . 欧共体50UDP 的 β-甲基酯及其 2-硫代类似物的值分别为 2730 和 56 nM。β-叔的丁基酯4是11倍UDPG更有效，但β-芳氧基或更大，β支链烷基酯，例如环己基，不太有效。UDP 与刚性北或南甲氧基碳（双环 [3.1.0] 己烷） 组的核糖替代消除了 P2Y 14受体激动剂活性。α,β-亚甲基和二氟亚甲基对 P2Y 14
• Method of producing nucleic acid molecules with reduced secondary structure
  申请人：Agilent Technologies, Inc.

  公开号：EP1624059A2

  公开（公告）日：2006-02-08

  The present invention provides a system for generating nucleic acid molecules having a reduced ability to hybridize to form intermolecular and intramolecular base pairs between regions of substantial complementarity as compared with nucleic acid molecules having the same nucleotide sequence containing naturally-occurring nucleotides. Furthermore, nucleic acid molecules of the present invention are characterized by the ability to form intermolecular base pairs with other nucleic acid molecules of choice.

  本发明提供了一种生成核酸分子的系统，与具有相同核苷酸序列、含有天然存在的核苷酸的核酸分子相比，本发明的核酸分子具有较低的杂交能力，能够在具有实质性互补性的区域之间形成分子间和分子内碱基对。此外，本发明核酸分子的特点是能够与所选择的其他核酸分子形成分子间碱基配对。
• Synthesis and Structure−Activity Relationships of Uracil Nucleotide Derivatives and Analogues as Agonists at Human P2Y₂, P2Y₄, and P2Y₆ Receptors
  作者：Ali El-Tayeb、Aidong Qi、Christa E. Müller

  DOI：10.1021/jm060848j

  日期：2006.11.30

  A series of UTP, UDP, and UMP derivatives and analogues were synthesized and evaluated at the human pyrimidinergic P2Y receptor subtypes P2Y(2), P2Y(4), and P2Y(6) stably expressed in 1321N1 astrocytoma cells. Substituents at N3 of UTP were poorly tolerated by P2Y2 and P2Y4 receptors. In contrast, a large phenacyl substituent at N3 of UDP was well tolerated by the P2Y6 receptor, yielding a potent and selective P2Y6 receptor agonist (3-phenacyl-UDP, EC50 = 70 nM, > 500-fold selective). The most potent and selective P2Y2 receptor agonist of the present series was 2-thio-UTP (EC50 = 50 nM, >= 30-fold selective vs P2Y(4) and P2Y6). All modifications at the uracil base of UTP led to a decrease in potency at the P2Y4 receptor. A beta,gamma-dichloromethylene modification in the triphosphate chain of 5-bromo-UTP was tolerated by all three receptor subtypes, thus opening up a new strategy to obtain ectonucleotide diphosphohydrolase- and phosphatase-resistant P2Y(2), P2Y(4), and P2Y(6) receptor agonists.
• Active Site Probes for Yeast OMP Decarboxylase: Inhibition Constants of UMP and Thio-Substituted UMP Analogues and Greatly Reduced Activity toward CMP-6-Carboxylate
  作者：Jeffrey A. Smiley、Lana Saleh

  DOI：10.1006/bioo.1999.1140

  日期：1999.8

  The catalytic mechanism of orotidine-5'-monophosphate decarboxylase (ODCase, EC 4.1.1.23) involves a proton-sensitive step, probably proton donation to one of the carbonyl oxygens of the substrate, and may also include participation of a Zn2+ ion. To probe the active site for these mechanistic features, thio-substituted analogues of the product UMP were used as inhibitors of yeast ODCase. The intrinsic inhibition constants of the anionic pyrimidines were calculated using the measured inhibition constants and the pK(a) values of the respective compounds. 4-ThioUMP is a stronger inhibitor than UMP, while 2-thioUMP has a K-i virtually the same as that for UMP. A potential alternate substrate, CMP-6-carboxylate, has been synthesized and found to have undetectable activity and weak binding to ODCase. The results are discussed in a unified model for catalysis involving protonation at O2 and a proposed Zn2+ interaction at O4, (C) 1999 Academic Press.
• Thiouridylic acid formation and bacterial growth
  作者：Harold Amos、Elizabeth Vollmayer、Morton Korn

  DOI：10.1016/0003-9861(58)90062-6

  日期：1958.9