[[[[(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲氧基-羟基磷酰]氧基-羟基磷酰]氧基-羟基磷酰][(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲基磷酸氢酯 | 5542-28-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （5'->5'）-二核苷酸
• 中文名称: [[[[(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲氧基-羟基磷酰]氧基-羟基磷酰]氧基-羟基磷酰][(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲基磷酸氢酯
• 英文名称: Diadenosine tetraphosphate
• 英文别名: diadenosine 5',5'-tetraphosphate；[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate
• CAS: 5542-28-9
• 化学式: C₂₀H₂₈N₁₀O₁₉P₄
• 分子量: 836.393
• InChiKey: YOAHKNVSNCMZGQ-XPWFQUROSA-N

物化性质

• 沸点：
  1250.6±75.0 °C(Predicted)
• 密度：
  2.61±0.1 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -8.3
• 重原子数：
  53
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  434
• 氢给体数：
  10
• 氢受体数：
  27

反应信息

• 作为反应物：
  描述：

  [[[[(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲氧基-羟基磷酰]氧基-羟基磷酰]氧基-羟基磷酰][(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲基磷酸氢酯 在 Arabidopsis thaliana Hint₄ 作用下， 生成 二磷酸腺苷
  参考文献：
  名称：

  Dual activity of certain HIT-proteins:A. thalianaHint4 andC. elegansDcpS act on adenosine 5′-phosphosulfate as hydrolases (forming AMP) and as phosphorylases (forming ADP)

  摘要：

  Histidine triad (HIT)‐family proteins interact with different mono‐ and dinucleotides and catalyze their hydrolysis. During a study of the substrate specificity of seven HIT‐family proteins, we have shown that each can act as a sulfohydrolase, catalyzing the liberation of AMP from adenosine 5′‐phosphosulfate (APS or SO4‐pA). However, in the presence of orthophosphate, Arabidopsis thaliana Hint4 and Caenorhabditis elegans DcpS also behaved as APS phosphorylases, forming ADP. Low pH promoted the phosphorolytic and high pH the hydrolytic activities. These proteins, and in particular Hint4, also catalyzed hydrolysis or phosphorolysis of some other adenylyl‐derivatives but at lower rates than those for APS cleavage. A mechanism for these activities is proposed and the possible role of some HIT‐proteins in APS metabolism is discussed.

  DOI：

  10.1016/j.febslet.2009.11.003
• 作为产物：
  描述：

  5’-三磷酸腺苷 在 L-赖氨酸 、 lysyl tRNA synthetase (LysU) 、 TRIS buffer pH 8 、 potassium chloride 、 magnesium chloride 、 zinc(II) chloride 作用下， 生成 [[[[(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲氧基-羟基磷酰]氧基-羟基磷酰]氧基-羟基磷酰][(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲基磷酸氢酯
  参考文献：
  名称：

  Characterisation of stress protein LysU. Enzymic synthesis of diadenosine 5′,5‴-P¹,P⁴-tetraphosphate (Ap₄A) analogues by LysU

  摘要：

  The stress protein LysU (lysyl tRNA synthetase) has been purified from a recombinant strain of Escherichia coli expressing the plasmid pXLys5, and kinetically characterised. Preparative syntheses of analogues of the biologically important molecule diadenosine 5',5'''-P-1,P-4-tetraphosphate (Ap(4)A) are then achieved in good yield by enzyme catalysis, using purified LysU.

  DOI：

  10.1039/p19960002009

文献信息

• [EN] NOVEL SYNTHETIC DINUCLEOSIDE POLYPHOSPHATE ANALOGS AND THEIR USE AS NEW THERAPEUTIC AND/OR DIAGNOSTIC MODALITIES<br/>[FR] NOUVEAUX ANALOGUES SYNTHÉTIQUES DE DINUCLÉOSIDE POLYPHOSPHATE ET LEUR UTILISATION COMME NOUVELLES MODALITÉS THÉRAPEUTIQUES ET/OU DIAGNOSTIQUES
  申请人：ZATA PHARMACEUTICALS INC

  公开号：WO2010056795A1

  公开（公告）日：2010-05-20

  The invention provides novel synthetic dinucleoside polyphosphate analogs and their use as therapeutic compounds and/or diagnostic tools for the treatment and diagnosis of various human diseases and metabolic disorders.

  这项发明提供了新型合成二核苷酸聚磷酸盐类似物及其作为治疗化合物和/或诊断工具用于治疗和诊断各种人类疾病和代谢紊乱。
• Lipophilic Modifications to Dinucleoside Polyphosphates and Nucleotides that Confer Antagonist Properties at the Platelet P2Y₁₂ Receptor
  作者：James G. Douglass、Roshni I. Patel、Benjamin R. Yerxa、Sammy R. Shaver、Paul S. Watson、Krzysztof Bednarski、Robert Plourde、Catherine C. Redick、Kurt Brubaker、Arthur C. Jones、José L. Boyer

  DOI：10.1021/jm701348d

  日期：2008.2.1

  discovered that modification of natural and synthetic dinucleoside polyphosphates and nucleotides with lipophilic substituents on the ribose and base conferred P2Y12 receptor antagonist properties to these molecules producing potent inhibitors of ADP-mediated platelet aggregation. We describe methods for the preparation of these functionalized dinucleoside polyphosphates and nucleotides and report their

  血小板P2Y12受体在血小板功能的调节中起着核心作用，通过用氯吡格雷等药物治疗抑制该受体可导致血栓形成事件的减少。我们发现，天然和合成的二核苷多磷酸酯和核糖和碱基上具有亲脂性取代基的核苷酸修饰赋予这些分子产生P2Y12受体拮抗剂的特性，从而产生了有效的ADP介导的血小板聚集抑制剂。我们描述了制备这些功能化的二核苷多磷酸盐和核苷酸的方法，并报告了它们的相关活性。通过分析这些结果并通过选择合成方法解构必要的结构元件，我们制备了一系列高度官能化的核苷酸，
• What is the conformation of physiologically-active dinucleoside polyphosphates in solution? Conformational analysis of free dinucleoside polyphosphates by NMR and molecular dynamics simulations
  作者：Noa Stern、Dan Thomas Major、Hugo Emilio Gottlieb、Daniel Weizman、Bilha Fischer

  DOI：10.1039/c005122e

  日期：——

  indicated by NMR. The conformation around the glycosidic angle in NpnN′s was found to be anti/high anti and the preferred conformation around the C4′–C5′, C5′–O5′ bonds was found to be gauche–gauche (gg). The ribose moiety in NpnN′s showed a small preference for the S conformation, but when attached to cytosine the ribose ring preferred the N conformation. However, no predominant conformation was observed

  二核苷多磷酸盐或二核苷酸（Np n N'； N，N'= A，U，G，C；n = 2-7）是天然存在的生理活性化合物。尽管对二核苷酸的兴趣以及它们的构象与其生物学功能的相关性，但是对二核苷酸的构象的研究还不够充分。因此，在这里，我们通过各种NMR技术对一系列Np n N'Na +盐（N = A，G，U，C； N'= A，G，U，C；n = 2–5）进行了构象分析。。如NMR所示，除Up 4/5 U外，所有研究的二核苷酸均在水溶液中形成分子内碱基堆积相互作用。Np n中糖苷角周围的构象发现N's是抗/高抗性，并且发现C4'-C5'，C5'-O5'键周围的优选构象是gauche – gauche（gg）。Np n N's中的核糖部分显示出对S构象的偏爱，但是当连接到胞嘧啶时，核糖环则优先选择N构象。然而，在任何二核苷酸中均未观察到核糖部分的主要构象。Ap 2 A和Ap 4 A Na +盐的分子动力学模拟支持了实验结果。此外，针对Ap
• Hydrolytic reactions of diadenosine 5′,5′-triphosphate
  作者：Satu Mikkola

  DOI：10.1039/b313200e

  日期：——

  been studied over a wide pH-range. Under acidic conditions the reaction shows a first-order dependence on the hydronium ion concentration. Below pH 3 the rate-increase begins to level off. From pH 6 to 9 the hydrolysis is slow and pH-independent. Base-catalysed hydrolysis is observed in NaOH-solutions. Under alkaline conditions an intramolecular nucleophilic attack on the phosphate producing 3',5'-cAMP

  已在较宽的pH范围内研究了腺苷5'，5'-三磷酸水解为AMP和ADP的过程。在酸性条件下，反应显示出对水合氢离子浓度的一级依赖性。pH低于3时，速率增加开始趋于平稳。从pH 6到9，水解缓慢且不依赖pH。在NaOH溶液中观察到碱催化的水解。在碱性条件下，还观察到分子内亲核性攻击产生磷酸盐的3'，5'-cAMP，但它比分子间反应慢。腺苷部分的去纯化在酸性和碱性条件下都与水解竞争，但是机理不同。在酸性条件下研究了Ap（3）A水解和腺苷部分的去纯化的温度依赖性，并计算了反应的活化参数。这项工作的结果反映了一个事实，即带负电荷的聚磷酸盐基团对亲核攻击非常有抵抗力。仅在酸性条件下才能观察到有效的催化作用，在该条件下磷酸基团会质子化。一般的酸或碱不催化水解。此外，仅在高碱浓度下观察到氢氧根离子催化的裂解，而其他带负电荷的亲核试剂未攻击多腺苷多磷酸的磷酸基团。一般的酸或碱不催化水解。此外，仅在高碱浓度下
• Engineering Human Fhit, a Diadenosine Triphosphate Hydrolase, into an Efficient Dinucleoside Polyphosphate Synthase
  作者：Kaisheng Huang、Perry A. Frey

  DOI：10.1021/ja0400640

  日期：2004.8.1

  dinucleoside polyphosphates. Fhit catalyzes the Mg2+-dependent hydrolysis of P1-5'-O-adenosine-P3-5'-O-adenosine triphosphate (Ap3A) to AMP and MgADP. Mutation of His96 to glycine disables Fhit as a catalyst for the hydrolysis of phosphoanhydrides such as Ap3A. However, the mutated enzyme H96G-Fhit efficiently catalyzes the synthesis of phosphoanhydride bonds in reactions of nucleoside-5'-phosphimidazolides

  假定的人类肿瘤抑制基因 FHIT 编码 Fhit，即脆弱的组氨酸三联体蛋白。Fhit 被认为参与涉及双核苷多磷酸的信号转导途径。Fhit 催化 P1-5'-O-腺苷-P3-5'-O-三磷酸腺苷 (Ap3A) 依赖 Mg2+ 水解为 AMP 和 MgADP。His96 突变为甘氨酸会使 Fhit 作为磷酸酐（如 Ap3A）水解的催化剂失效。然而，突变酶 H96G-Fhit 在核苷 5'-磷咪唑化物与核苷二磷酸和三磷酸的反应中有效催化磷酸酐键的合成。H96G-Fhit 可用于合成多种二核苷三磷酸和四磷酸。我们在此描述了使用 H96G-Fhit 催化 Ap3A、Ap3C、Ap3G、Ap3T、Ap3U、Cp3U、Tp3U、dAp3U、Ap4A、