生物素五聚乙二醇乙基叠氮 | 1163732-89-5

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 中文名称: 生物素五聚乙二醇乙基叠氮
• 英文名称: N-(17-azido-3,6,9,12,15-pentaoxaheptadecyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-pentanamide
• 英文别名: Biotin-PEG5-azide；5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethyl]pentanamide
• CAS: 1163732-89-5
• 化学式: C₂₂H₄₀N₆O₇S
• 分子量: 532.662
• InChiKey: MKXKDMBFPMTVAW-ZJOUEHCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  36
• 可旋转键数：
  23
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  156
• 氢给体数：
  3
• 氢受体数：
  10

安全信息

• 储存条件：
  2-8°C

制备方法与用途

Biotin-PEG5-azide是一种基于PEG结构的PROTAC连接子，可用于制备PROTAC。

反应信息

• 作为反应物：
  描述：

  生物素五聚乙二醇乙基叠氮 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以88%的产率得到生物素-PEG5-胺
  参考文献：
  名称：

  Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A

  摘要：

  《摘要》 癌症外泌体分泌的抑制剂，可以促进癌症进展和转移，不仅可以加快外泌体生物学研究，还可以为癌症患者提供治疗益处。在这里，我们确定了磺胺噻唑（SFX）作为乳腺癌细胞分泌小胞外囊泡（sEV）的抑制剂，通过干扰内皮素受体A（ETA）。SFX是一种FDA批准的口服抗生素，在乳腺癌移植小鼠模型中显示出显著的抗肿瘤和抗转移效果，减少了与sEV生物发生和分泌有关的蛋白质的表达，并触发了多囊内体与溶酶体的共定位以进行降解。我们通过增强和减弱ETA蛋白的功能研究，通过直接结合分析，以及药理学和遗传学方法，证明了ETA作为SFX靶点的重要作用。这些发现可能为sEV靶向癌症治疗和sEV生物学的机制研究奠定基础。

  DOI：

  10.1038/s41467-019-09387-4
• 作为产物：
  描述：

  D-生物素 、 17-叠氮-3,6,9,12,15-五氧杂十七烷-1-胺 在 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 作用下， 以 甲醇 为溶剂， 以57%的产率得到生物素五聚乙二醇乙基叠氮
  参考文献：
  名称：

  Role of Linkers in Tertiary Amines That Mediate or Catalyze 1,3,5-Triazine-Based Amide-Forming Reactions

  摘要：

  We studied 1,3,5-triazine-based amide-forming reactions that are mediated or catalyzed by various tert-amines. The representative tert-amine was trimethylamine, which has amido, 1,2,3-triazolyl, aryl, and alkyl linkers. It was found that electron-deficient aryl and heteroaryl linkers, particularly 1,2,3-triazolyl linkers, are superior. On the basis of our findings, we synthesized ligand catalysts, including a 1,2,3-triazolyl linker that connects a protein ligand to a trimethylamine moiety, and found that fluorescent-labeling of a targeting protein using the ligand catalysts proceeded in good yields.

  DOI：

  10.1021/jo500376m

文献信息

• Synthesis and antitumor activity of biotinylated camptothecin derivatives as potent cytotoxic agents
  作者：Cheng-Ting Zi、Liu Yang、Feng-Qing Xu、Fa-Wu Dong、Rui-Jing Ma、Yan Li、Jun Zhou、Zhong-Tao Ding、Zi-Hua Jiang、Jiang-Miao Hu

  DOI：10.1016/j.bmcl.2018.11.049

  日期：2019.1

  designed and synthesized. The key to the synthesis was achieved by employing an esterification reaction and click chemistry. All of the new derivatives were tested for cytotoxicity against five human tumor cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480 with IC50 values ranging from 0.13 to 21.53 μM. Most of the derivatives exhibited potent cytotoxicity, especially compound 17 (IC50 = 0

  设计并合成了一系列生物素化喜树碱衍生物。合成的关键是通过酯化反应和点击化学来实现的。测试了所有新衍生物对五种人类肿瘤细胞系的细胞毒性，包括HL-60，SMMC-7721，A-549，MCF-7和SW480，IC 50值为0.13至21.53μM。大多数衍生物表现出强的细胞毒性，尤其是化合物17（IC 50  = 0.13–3.31μM）和化合物18（IC 50  = 0.23–1.48μM），具有最高的细胞毒性。讨论了生物素化喜树碱衍生物的结构-活性关系（SAR），以探索新型抗癌药。
• Dual-channel near-infrared fluorescent probe for real-time tracking of endogenous γ-glutamyl transpeptidase activity
  作者：Bing Bai、Chenxu Yan、Yutao Zhang、Zhiqian Guo、Wei-Hong Zhu

  DOI：10.1039/c8cc07376g

  日期：——

  We developed a curcuminoid difluoroboron-based fluorescent probe for tracking endogenous GGT activity with dual-channel light-up near-infrared (NIR) imaging.

  我们开发了一种基于姜黄素二氟硼的荧光探针，用于追踪内源性GGT活性，并通过双通道近红外成像实现光亮。
• Discovery of an H3K36me3-Derived Peptidomimetic Ligand with Enhanced Affinity for Plant Homeodomain Finger Protein 1 (PHF1)
  作者：Isabelle A. Engelberg、Jiuyang Liu、Jacqueline L. Norris-Drouin、Stephanie H. Cholensky、Samantha A. Ottavi、Stephen V. Frye、Tatiana G. Kutateladze、Lindsey I. James

  DOI：10.1021/acs.jmedchem.1c00430

  日期：2021.6.24
• Role of Linkers in Tertiary Amines That Mediate or Catalyze 1,3,5-Triazine-Based Amide-Forming Reactions
  作者：Masanori Kitamura、Fumitaka Kawasaki、Kouichi Ogawa、Shuichi Nakanishi、Hiroyuki Tanaka、Kohei Yamada、Munetaka Kunishima

  DOI：10.1021/jo500376m

  日期：2014.4.18

  We studied 1,3,5-triazine-based amide-forming reactions that are mediated or catalyzed by various tert-amines. The representative tert-amine was trimethylamine, which has amido, 1,2,3-triazolyl, aryl, and alkyl linkers. It was found that electron-deficient aryl and heteroaryl linkers, particularly 1,2,3-triazolyl linkers, are superior. On the basis of our findings, we synthesized ligand catalysts, including a 1,2,3-triazolyl linker that connects a protein ligand to a trimethylamine moiety, and found that fluorescent-labeling of a targeting protein using the ligand catalysts proceeded in good yields.
• Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A
  作者：Eun-Ju Im、Chan-Hyeong Lee、Pyong-Gon Moon、Gunassekaran Gowri Rangaswamy、Byungheon Lee、Jae Man Lee、Jae-Chul Lee、Jun-Goo Jee、Jong-Sup Bae、Taeg-Kyu Kwon、Keon-Wook Kang、Myeong-Seon Jeong、Joo-Eun Lee、Hyun-Suk Jung、Hyun-Joo Ro、Sangmi Jun、Wonku Kang、Seung-Yong Seo、Young-Eun Cho、Byoung-Joon Song、Moon-Chang Baek

  DOI：10.1038/s41467-019-09387-4

  日期：——

  Inhibitors of the secretion of cancer exosomes, which promote cancer progression and metastasis, may not only accelerate exosome biology research but also offer therapeutic benefits for cancer patients. Here we identify sulfisoxazole (SFX) as an inhibitor of small extracellular vesicles (sEV) secretion from breast cancer cells through interference with endothelin receptor A (ETA). SFX, an FDA-approved oral antibiotic, showed significant anti-tumor and anti-metastatic effects in mouse models of breast cancer xenografts, the reduced expression of proteins involved in biogenesis and secretion of sEV, and triggered co-localization of multivesicular endosomes with lysosomes for degradation. We demonstrate the important role of ETA, as target of SFX, by gain- and loss-of-function studies of the ETA protein, through a direct binding assay, and pharmacological and genetic approaches. These findings may provide a foundation for sEV-targeted cancer therapies and the mechanistic studies on sEV biology.

  《摘要》 癌症外泌体分泌的抑制剂，可以促进癌症进展和转移，不仅可以加快外泌体生物学研究，还可以为癌症患者提供治疗益处。在这里，我们确定了磺胺噻唑（SFX）作为乳腺癌细胞分泌小胞外囊泡（sEV）的抑制剂，通过干扰内皮素受体A（ETA）。SFX是一种FDA批准的口服抗生素，在乳腺癌移植小鼠模型中显示出显著的抗肿瘤和抗转移效果，减少了与sEV生物发生和分泌有关的蛋白质的表达，并触发了多囊内体与溶酶体的共定位以进行降解。我们通过增强和减弱ETA蛋白的功能研究，通过直接结合分析，以及药理学和遗传学方法，证明了ETA作为SFX靶点的重要作用。这些发现可能为sEV靶向癌症治疗和sEV生物学的机制研究奠定基础。