guanosine-5‘-O-(α,β-methylene)diphosphate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: guanosine-5‘-O-(α,β-methylene)diphosphate
• 英文别名: guanosine-5'-O-[(phosphonomethyl)phosphonic acid]；guanosine 5'-methylene bisphosphonate；Phosphomethylphosphonic acid guanosyl ester；[[(2R,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid
• 化学式: C₁₁H₁₇N₅O₁₀P₂
• 分子量: 441.231
• InChiKey: OCJWYBKRHNXUME-KQYNXXCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  239
• 氢给体数：
  7
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  guanosine-5‘-O-(α,β-methylene)diphosphate 在 2,2'-二硫二吡啶 、 三乙胺 、 三苯基膦 、 zinc(II) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成
  参考文献：
  名称：

  帽类似物及其合成方法和mRNA

  摘要：

  本发明涉及化学合成技术领域，尤其涉及帽类似物及其合成方法和mRNA。帽类似物的合成方法包括以下步骤：S1、以鸟苷为原料，通过上甲基反应、磷酸化反应后，将得到的产物与咪唑反应获得中间产物，利用中间产物制备得到所述帽类似物。在合成过程中各个中间体稳定性较强，获得的帽类似物产品产量较高，将本发明的帽类似物应用于mRNA中，利于提高mRNA稳定性，进一步提高转录效率和加帽率。

  公开号：

  CN117567528A
• 作为产物：
  描述：

  鸟苷 在 磷酸三甲酯 、 三乙基碳酸氢铵缓冲液 作用下， 以 水 为溶剂， 生成 guanosine-5‘-O-(α,β-methylene)diphosphate
  参考文献：
  名称：

  2位取代的α，β-亚甲基ADP衍生物：具有可变结合模式的强效竞争性Ecto-5'-核苷酸酶（CD73）抑制剂。

  摘要：

  CD73抑制剂是用于癌症（免疫）治疗的有前途的药物。在这里，我们介绍了合成，结构-活性关系，和竞争性CD73抑制剂α，β-亚甲基-ADP（AOPCP）取代2位的新型衍生物的共晶体结构。小极性或亲脂性残基增加了效力，2-碘-和2-氯腺苷-5'-O-[（膦酰基甲基）膦酸]（15、16）是对人CD73的Ki值为3-的最有效抑制剂6 nM。取决于2-取代基的大小和性质，通过X射线晶体学观察到可变的结合模式。取决于结合模式，发现了较大的物种差异，例如，2-哌嗪基-AOPCP（21）与人CD73相比，对大鼠CD73的效力低> 12倍。这项研究表明，只需将一个小的取代基引入AOPCP的2位即可实现高CD73抑制力，而无需额外的大体积N6-取代基。此外，它为竞争性CD73抑制剂的结合模式提供了宝贵的见解，为药物开发提供了极好的基础。

  DOI：

  10.1021/acs.jmedchem.9b01611

文献信息

• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• ppGpp analogues inhibit synthetase activity of Rel proteins from Gram-negative and Gram-positive bacteria
  作者：Ezequiel Wexselblatt、Jehoshua Katzhendler、Raspudin Saleem-Batcha、Guido Hansen、Rolf Hilgenfeld、Gad Glaser、Roee R. Vidavski

  DOI：10.1016/j.bmc.2010.04.064

  日期：2010.6.15

  A prominent feature of the stringent response is the accumulation of two unusual phosphorylated derivatives of GTP and GDP (pppGpp: 5'-triphosphate-3'-diphosphate, and ppGpp: 5'-3'-bis-diphosphate), collectively called (p) ppGpp, within a few seconds after the onset of amino-acid starvation. The synthesis of these 'alarmone' compounds is catalyzed by RelA homologues. Other features of the stringent response include inhibition of stable RNA synthesis and modulation of transcription, replication, and translation. (p) ppGpp accumulation is important for virulence induction, differentiation and antibiotic resistance. We have synthesized a group of (p) ppGpp analogues and tested them as competitive inhibitors of Rel proteins in vitro. 2'-Deoxyguanosine-3'-5'-di(methylene bisphosphonate) [compound (10)] was found as an inhibitor that reduces ppGpp formation in both Gram-negative and Gram-positive bacteria. In silico docking together with competitive inhibition analysis suggests that compound (10) inhibits activity of Rel proteins by competing with GTP/GDP for its binding site.As Rel proteins are completely absent in mammalians, this appears to be a very attractive approach for the development of novel antibacterial agents. (C) 2010 Elsevier Ltd. All rights reserved.
• 2-(4-Nitrophenyl)ethyl Methylenebis(phosphonate):  A Versatile Reagent for the Synthesis of Nucleoside 5‘-Methylenebis(phosphonate)s
  作者：Krystyna Lesiak、Kyoichi A. Watanabe、Jay George、Krzysztof W. Pankiewicz

  DOI：10.1021/jo971859a

  日期：1998.3.1

  2-(4-Nitrophenyl)ethyl methylenebis(phosphonate) (6) was prepared by reaction of equimolar amounts of 2-(4-nitrophenyl)ethyl alcohol and methylenebis(phosphonyl) tetrachloride in the presence of tetrazole. Compound 6 was further converted into the corresponding 4-nitrophenylethyl trisanhydride intermediate 7 by dehydration with diisopropylcarbodiimide (DIC). Reaction of 7 with either 2',3'-O-isopropylideneadenosine (8a) or 2',3'-O-isopropylideneguanosine (8b) afforded, after hydrolysis, the desired P-1-[2-(4-nitrophenyl)ethyl]-P-2-(2',3'-O-isopropylideneadenosin-5'-yl)methylenebis(phosphonate) (9a) and guanosine analogue 9b, respectively. A similar treatment of intermediate 7 with 3'-O-acetylthymidine (12a), 3'-O-acetyl-2'-deoxy-N-4-benzoylcytidine (12b), 3'-O-acetyl-2'-deoxy-N-6-benzoyladenosine (12c), and 3'-O-acetyl-2'-deoxy-N-2-isobutyrylguanosine (12d) gave the corresponding 2-(4-nitrophenyl)ethyl methylenebis(phosphonate)s 13a-d. These compounds as well as 9a,b were treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) which caused elimination of the 2-(4-nitrophenyl)ethyl group. The base labile 3'-O-acetyl, N-4-acetyl, N-6-benzoyl, and N-2-isobutyryl groups of 12a-d were also removed during the DBU treatment. Thus, the 5'-methylenebis(phosphonate)s of 2',3'-O-isopropylideneadenosine (10a), 2',3'-O-isopropylideneguanosine (10b), thymidine (14a), 2'-deoxycytidine (14b), 2'-deoxyadenosine (14c), and 2'-deoxyguanosine (14d) were prepared in good yield. De-O-isopropylidenation of 10a and 10b afforded adenosine 5'-methylenebis(phosphonate) (11a) and guanosine 5'-methylenebis(phosphonate) (11b), respectively.
• ADVANCED DRUG DEVELOPMENT AND MANUFACTURING
  申请人：Los Alamos National Security, LLC

  公开号：EP2084519A2

  公开（公告）日：2009-08-05
• X-RAY FLUORESCENCE ANALYSIS METHOD
  申请人：Los Alamos National Security, LLC

  公开号：EP2084519B1

  公开（公告）日：2012-08-01