尿苷 3',5'-环单磷酸酯 | 4004-57-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 尿苷 3',5'-环单磷酸酯
• 中文别名: 尿苷3',5'-环单磷酸酯
• 英文名称: uridine 3',5'-cyclic monophosphate
• 英文别名: Uridin-3',5'-cyclophosphat；CUMP；uridine 3′,5′-cyclic monophosphate；3′,5′-cUMP；Uridin-3',5'-cycl. Phosphat；Uridin-3',5'-cyclisches Phosphat；Cyclic-3',5'-UMP；1-[(4aR,6R,7R,7aS)-2,7-dihydroxy-2-oxo-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]pyrimidine-2,4-dione
• CAS: 4004-57-3
• 化学式: C₉H₁₁N₂O₈P
• 分子量: 306.169
• InChiKey: NXIHNBWNDCFCGL-XVFCMESISA-N

物化性质

• 密度：
  1.85±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  尿苷 3',5'-环单磷酸酯 在 乙二胺四乙酸 、 recombinant N-terminally GST-tagged human cardiac phosphodiesterase PDE3A (484–1141) 、 magnesium chloride 、 BSA 作用下， 以 aq. buffer 为溶剂， 反应 0.25h， 生成 尿苷5-单磷酸
  参考文献：
  名称：

  cUMP被PDE3A水解。

  摘要：

  如先前报道，心脏磷酸二酯酶PDE3A水解cUMP。此外，几十年前在牛和狗的心脏中检测到了cUMP降解活性。我们的目的是表征PDE3A介导的cUMP水解的酶动力学参数，并研究心肌细胞中是否存在cUMP和cUMP水解的PDE。在时程，抑制剂和Michaelis-Menten动力学实验中对PDE3A介导的cUMP水解进行了表征。在新生大鼠心肌细胞（NRCM）和小鼠HL-1心肌细胞中定量细胞内环状核苷酸（cNMP）浓度和降解cUMP的PDE的mRNA。此外，我们研究了HL-1细胞匀浆和完整细胞中cUMP的降解。通过HPLC耦合串联质谱法检测PDE反应的离析物（cNMPs）和产物（NMPs）。PDE3A降解的cUMP（UMP形成的测量值）的KM值为〜143μM，V max值为〜42μmol/ min / mg。PDE3A水解的cAMP的KM值为〜0.7μM，V max为〜1.2μmol/ min /

  DOI：

  10.1007/s00210-016-1328-1
• 作为产物：
  描述：

  尿苷-5'-三磷酸 在 manganese(II) chloride tetrahydrate 、 full-length adenylyl cyclase toxin edema factor from Bacillus anthracis 作用下， 反应 0.5h， 生成 尿苷 3',5'-环单磷酸酯
  参考文献：
  名称：

  Cytidylyl and Uridylyl Cyclase Activity of Bacillus anthracis Edema Factor and Bordetella pertussis CyaA

  摘要：

  Cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) are second messengers for numerous mammalian cell functions. The natural occurrence and synthesis of a third cyclic nucleotide (cNMP), cyclic cytidine 3',5'-monophosphate (cCMP), is a matter of controversy, and almost nothing is known about, cyclic uridine 3',5'-monophosphate (cUMP). Bacillus anthracis and Bordetella pertussis secrete the adenylyl cyclase (AC) toxins edema factor (EF) and CyaA, respectively, weakening immune responses and facilitating bacterial proliferation. A cell-permeable cCMP analogue inhibits human neutrophil superoxide production. Here, we report that EF and CyaA also possess cytidylyl cyclase (CC) and uridylyl cyclase (UC) activity. CC and UC activity was determined by a radiometric assay, using [alpha-P-32]CTP and [alpha-P-32]UTP as substrates, respectively, and by a high-performance liquid chromatography method. The identity of cNMPs was confirmed by mass spectrometry. On the basis of available crystal structures, we developed a model illustrating conversion of CTP to cCMP by bacterial toxins. In conclusion, we have shown both El: and CyaA have a rather broad substrate specificity and exhibit cytidylyl and uridylyl cyclase activity. Both cCMP and cUMP may contribute to toxin actions.

  DOI：

  10.1021/bi100684g

文献信息

• Membrane-Permeable Octanoyloxybenzyl-Masked cNMPs As Novel Tools for Non-Invasive Cell Assays
  作者：Alexandra Ruthenbeck、Elisa Marangoni、Björn-Ph. Diercks、Aileen Krüger、Alexander Froese、Nadja Bork、Viacheslav Nikolaev、Andreas Guse、Chris Meier

  DOI：10.3390/molecules23112960

  日期：——

  Adenine nucleotide (AN) 2nd messengers, such as 3′,5′-cyclic adenosine monophosphate (cAMP), are central elements of intracellular signaling, but many details of their underlying processes remain elusive. Like all nucleotides, cyclic nucleotide monophosphates (cNMPs) are net-negatively charged at physiologic pH which limits their applicability in cell-based settings. Thus, many cellular assays rely on sophisticated techniques like microinjection or electroporation. This setup is not feasible for medium- to high-throughput formats, and the mechanic stress that cells are exposed to raises the probability of interfering artefacts or false-positives. Here, we present a short and flexible chemical route yielding membrane-permeable, bio-reversibly masked cNMPs for which we employed the octanoyloxybenzyl (OB) group. We further show hydrolysis studies on chemical stability and enzymatic activation, and present results of real-time assays, where we used cAMP and Ca2+ live cell imaging to demonstrate high permeability and prompt intracellular conversion of some selected masked cNMPs. Based on these results, our novel OB-masked cNMPs constitute valuable precursor-tools for non-invasive studies on intracellular signaling.

  腺嘌呤核苷酸（AN）第二信使，如3′,5′-环腺苷单磷酸（cAMP），是细胞内信号传导的中心元素，但其潜在过程的许多细节仍然不明确。像所有核苷酸一样，环核苷酸单磷酸（cNMPs）在生理pH下是净负电荷，这限制了它们在基于细胞的设置中的适用性。因此，许多细胞分析依赖于微注射或电穿孔等复杂技术。这种设置对于中高通量格式来说是不可行的，而细胞所受的机械应力增加了干扰性伪迹或假阳性的可能性。在这里，我们提出了一种简短灵活的化学途径，产生了可渗透膜、可生物逆转掩蔽的cNMPs，我们采用了辛酰氧基苯基（OB）基团。我们进一步展示了化学稳定性和酶促活化的水解研究，并呈现了实时分析结果，我们使用cAMP和Ca2+活细胞成像来展示一些选定掩蔽cNMPs的高渗透性和迅速的细胞内转化。基于这些结果，我们的新型OB掩蔽cNMPs构成了用于细胞内信号研究的有价值的前体工具。
• Immunoaffinity purification of cyclic nucleotide phosphodiesterase from Lactuca cotyledons
  作者：Donato Chiatante、Carlotta Balconi、Russell P. Newton、Eric G. Brown

  DOI：10.1016/0031-9422(88)87014-6

  日期：1988.1

  Abstract To facilitate further study of a multifunctional phosphodiesterase, previously partially purified from Lactuca cotyledons, a new purification step has been devised. This uses an immunoaffinity column based upon polyclonal antibodies raised against the partially purified enzyme. Preparation of the immunoaffinity column, purification of the enzyme using the new protocol, and analysis of the

  摘要 为了促进对先前从莴苣子叶中部分纯化的多功能磷酸二酯酶的进一步研究，设计了一个新的纯化步骤。这使用基于针对部分纯化酶产生的多克隆抗体的免疫亲和柱。描述了免疫亲和柱的制备、酶的纯化以及纯化酶活性的分析。额外的步骤产生了具有显着更高比活性并且不含核苷酸酶和非特异性磷酸酶活性的酶制剂。观察到的酶特性证实了与哺乳动物多功能磷酸二酯酶的相似性，但重申了 Lactuca 磷酸二酯酶上存在两种类型的底物结合位点。
• ODCASE INHIBITORS FOR THE TREATMENT OF MALARIA
  申请人：Kotra Lakshmi P.

  公开号：US20090221524A1

  公开（公告）日：2009-09-03

  The present invention includes methods of treating or preventing malaria by administering an anti-malarial effective amount of 6-substituted uridine derivatives to a subject need thereof. The invention also includes new 6-substituted uridine derivatives for use as therapeutics, in particular to treat malaria.

  本发明涉及通过向需要治疗或预防疟疾的受体施用抗疟疾有效量的6-取代尿嘧啶衍生物来治疗或预防疟疾的方法。本发明还包括新的6-取代尿嘧啶衍生物，用于作为治疗剂，特别是用于治疗疟疾。
• Pyrimidine Derivatives As Anticancer Agents
  申请人：Kotra Lakshmi P.

  公开号：US20100056468A1

  公开（公告）日：2010-03-04

  The present invention includes methods of treating or preventing cancer by administering an effective amount of 6-substituted pyrimidine derivatives of the Formula I to a subject need thereof:

  本发明涉及通过向需要该治疗的受体施用公式I的6-取代嘧啶衍生物的有效量来治疗或预防癌症的方法：
• ODCASE INHIBITORS AS ANTI-VIRALS AND ANTIBIOTICS
  申请人：Kotra Lakshmi P.

  公开号：US20100087388A1

  公开（公告）日：2010-04-08

  The present invention includes the utility of anti-viral and/or antibacterial effective amounts of 6-substituted nucleoside derivatives of formula (I) (e.g. 6-iodouridine and 6-iodouridine monophosphate) in the treatment or prevention of viral infections (e.g. Flavivridae, Bunyaviridae, or Togaviridae, or viral infections of hepatitis C, hepatitis B, herpes, influenza, HIV, polio, Coxsackie A/B, rhino, small pox, Ebola, West Nile, or corona virus) and/or bacterial infections (e.g. H. pylori, S. Aureus, B. anthracis, Mycobacterial tuberculosis, M. leprae, M. avium, P. aueruginosa, Streptococcal species, and Pneumocystis carinii ).

  本发明涉及式（I）的6-取代核苷衍生物（例如6-碘尿嘧啶和6-碘尿苷酸单磷酸盐）的抗病毒和/或抗细菌有效量的实用性，用于治疗或预防病毒感染（例如黄病毒科、布尼亚病毒科、托加病毒科或丙型肝炎、乙型肝炎、疱疹、流感、艾滋病毒、脊髓灰质炎、柯萨奇A/B病毒、鼻病毒、天花、埃博拉、西尼罗河或冠状病毒）和/或细菌感染（例如幽门螺杆菌、金黄色葡萄球菌、炭疽杆菌、结核分枝杆菌、麻风分枝杆菌、非结核分枝杆菌、铜绿假单胞菌、链球菌属和肺孢子菌）。