5'-O-[N-[L-leucyl]-sulfamoyl]adenosine | 288591-93-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 5'-O-[N-[L-leucyl]-sulfamoyl]adenosine
• 英文别名: (1Z,2S)-N-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxysulfonyl]-2-azaniumyl-4-methylpentanimidate
• CAS: 288591-93-5
• 化学式: C₁₆H₂₅N₇O₇S
• 分子量: 459.483
• InChiKey: XFEDFDTWJLGMBO-LEJQEAHTSA-N

物化性质

• 密度：
  1.83±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：49.17（最大浓度 mg/mL）；107.01（最大浓度 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  226
• 氢给体数：
  5
• 氢受体数：
  12

制备方法与用途

生物活性

Leu-AMS (化合物6)，一种亮氨酸类似物，是有效的亮氨酰-tRNA 合成酶 (LRS) 抑制剂，IC50 值为 22.34 nM。Leu-AMS 抑制了 LRS 的催化活性，但不影响亮氨酸诱导的 mTORC1 活化。此外，Leu-AMS 在癌细胞和正常细胞中显示出细胞毒性，并能够抑制细菌的生长。

靶点

• IC50: 22.34 nM (LRS)

体外研究

Leu-AMS 被证明是一种强效的亮氨酰-tRNA 合成酶 (LRS) 抑制剂，其 IC50 值为 22.34 nM。在体外实验中，Leu-AMS 在癌细胞和正常细胞中均显示出高度的细胞毒性，但不影响 S6 蛋白激酶（S6K）的磷酸化。尽管 Leu-AMS 抑制了 LRS 的催化活性，但它并不影响亮氨酸诱导的 mTORC1 激活。

反应信息

• 作为反应物：
  描述：

  5'-O-[N-[L-leucyl]-sulfamoyl]adenosine 、 formyl-methionyl-arginyl(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-threonyl(tBu)-glycyl-asparaginyl(trityl)-alanyl-OH 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl N-[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-5-[[amino-[(2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]-2-[[(2S)-2-formamido-4-methylsulfanylbutanoyl]amino]pentanoyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoyl]amino]acetyl]amino]-4-oxo-4-(tritylamino)butanoyl]amino]propanoyl]amino]-4-methylpentanoyl]sulfamate
  参考文献：
  名称：

  Extended targeting potential and improved synthesis of Microcin C analogs as antibacterials

  摘要：

  Microcin C (McC) (1) is a potent antibacterial compound produced by some Escherichia coli strains. McC functions through a Trojan-Horse mechanism: it is actively taken up inside a sensitive cell through the function of the YejABEF-transporter and then processed by cellular aminopeptidases. Processed McC (2) is a non-hydrolysable aspartyl-adenylate analog that inhibits aspartyl-tRNA synthetase (AspRS). A new synthesis is described that allows for the production of a wide variety of McC analogs in acceptable amounts. Using this synthesis a number of diverse compounds was synthesized with altered target specificity. Further characteristics of the YejABEF transporters were determined using these compounds. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.052
• 作为产物：
  描述：

  ((2R,3R,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-bis((tert-butyldimethylsilyl)oxy)tetrahydrofuran-2-yl)methyl sulfamate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 triethylamine tris(hydrogen fluoride) 、 三氟乙酸 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 5'-O-[N-[L-leucyl]-sulfamoyl]adenosine
  参考文献：
  名称：

  Extended targeting potential and improved synthesis of Microcin C analogs as antibacterials

  摘要：

  Microcin C (McC) (1) is a potent antibacterial compound produced by some Escherichia coli strains. McC functions through a Trojan-Horse mechanism: it is actively taken up inside a sensitive cell through the function of the YejABEF-transporter and then processed by cellular aminopeptidases. Processed McC (2) is a non-hydrolysable aspartyl-adenylate analog that inhibits aspartyl-tRNA synthetase (AspRS). A new synthesis is described that allows for the production of a wide variety of McC analogs in acceptable amounts. Using this synthesis a number of diverse compounds was synthesized with altered target specificity. Further characteristics of the YejABEF transporters were determined using these compounds. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.052

文献信息

• Extended targeting potential and improved synthesis of Microcin C analogs as antibacterials
  作者：Gaston H.M. Vondenhoff、Svetlana Dubiley、Konstantin Severinov、Eveline Lescrinier、Jef Rozenski、Arthur Van Aerschot

  DOI：10.1016/j.bmc.2011.07.052

  日期：2011.9

  Microcin C (McC) (1) is a potent antibacterial compound produced by some Escherichia coli strains. McC functions through a Trojan-Horse mechanism: it is actively taken up inside a sensitive cell through the function of the YejABEF-transporter and then processed by cellular aminopeptidases. Processed McC (2) is a non-hydrolysable aspartyl-adenylate analog that inhibits aspartyl-tRNA synthetase (AspRS). A new synthesis is described that allows for the production of a wide variety of McC analogs in acceptable amounts. Using this synthesis a number of diverse compounds was synthesized with altered target specificity. Further characteristics of the YejABEF transporters were determined using these compounds. (C) 2011 Elsevier Ltd. All rights reserved.