biotin N-succinimidyl ester | 1245615-71-7

• 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
• 英文名称: biotin N-succinimidyl ester
• 英文别名: 2,5-Dioxopyrrolidin-1-yl 5-((3aR,4R,6aS)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoate；(2,5-dioxopyrrolidin-1-yl) 5-[(3aR,4R,6aS)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoate
• CAS: 1245615-71-7
• 化学式: C₁₄H₁₉N₃O₅S
• 分子量: 341.388
• InChiKey: YMXHPSHLTSZXKH-JRKPZEMJSA-N

物化性质

• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  biotin N-succinimidyl ester 、 1-氨基-11-叠氮-3,6,9-三氧杂十一烷 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.25h， 生成 N-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)-5-((3aR,4R,6aS)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide
  参考文献：
  名称：

  Activity-Based Proteome Profiling of Potential Cellular Targets of Orlistat − An FDA-Approved Drug with Anti-Tumor Activities

  摘要：

  Orlistat, or tetrahydrolipstatin (THL), is an FDA-approved antiobesity drug with potential antitumor activities. Cellular off-targets and potential side effects of Orlistat in cancer therapies, however, have not been extensively explored thus far. In this study, we report the total of synthesis of THL-like protein-reactive probes, in which extremely conservative modifications (i.e., an alkyne handle) were introduced in the parental THL structure to maintain the native biological properties of Orlistat, while providing the necessary functionality for target identification via the bio-orthogonal click chemistry. With these natural productlike, cell-permeable probes, we were able to demonstrate, for the first time, this chemical proteomic approach is suitable for the identification of previously unknown cellular targets of Orlistat. In addition to the expected fatty acid synthase (FAS), we identified a total of eight new targets, some of which were further validated by experiments including Western blotting, recombinant protein expression, and site-directed mutagenesis. Our findings have important implications in the consideration of Orlistat as a potential anticancer drug at its early stages of development for cancer therapy. Our strategy should be broadly useful for off-target identification against quite a number of existing drugs and/or candidates, which are also covalent modifiers of their biological targets.

  DOI：

  10.1021/ja907716f
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 生物素杂质27 在 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 biotin N-succinimidyl ester
  参考文献：
  名称：

  2,2'：5'，2''-terthiophene-5-衍生物与蛋白质和单克隆抗体结合的新合成途径

  摘要：

  已经合成并表征了许多可以通过使用不同的官能团与蛋白质或其他载体分子连接的α-叔噻吩基-5-衍生物。描述了这些化合物中的一些与载体蛋白和抗体的缀合。

  DOI：

  10.1016/0040-4020(96)00654-0

文献信息

• Flexible and General Synthesis of Functionalized Phosphoisoprenoids for the Study of Prenylation in vivo and in vitro
  作者：Debapratim Das、Zakir Tnimov、Uyen T. T. Nguyen、Govindaraju Thimmaiah、Harriet Lo、Daniel Abankwa、Yaowen Wu、Roger S. Goody、Herbert Waldmann、Kirill Alexandrov

  DOI：10.1002/cbic.201100733

  日期：2012.3.19

  Prenylation probes: Eukaryotic protein prenyltransferases modify polypeptides with isoprenoid lipids. Modification of isoprenoids with reporter groups allows the creation of probes for the analysis of protein prenylation in vitro and in vivo. An amine‐derivatized isoprenoid scaffold was used as a novel starting point for the synthesis of functionalized phosphoisoprenoid libraries.

  异戊二烯基探针：真核蛋白异戊二烯基转移酶用类异戊二烯脂质修饰多肽。用报告基团修饰类异戊二烯可以创建用于体外和体内分析蛋白质异戊二烯化的探针。胺衍生化的类异戊二烯支架被用作合成功能化磷酸异戊二烯文库的新起点。
• Chemical Synthesis of the Trisaccharide Epitope of Phenolic Glycolipid-1 Surface Antigen from <i>Mycobacterium leprae</i>
  作者：Wan-Yue Luo、Bin Lu、Rong-Ye Zhou、Xiao Hu、Jin Wang

  DOI：10.1021/acs.joc.0c01088

  日期：2020.8.21

  PGL-1 epitope 1 bearing a p-aminoethylphenol group was efficiently synthesized by using linear synthetic routes. A method for efficient synthesis of oligosaccharides containing rhamnose rings was developed. The chemistry is flexible and could be used for the synthesis of other PGLs antigens. A biotinylated PGL-1 antigen 23 was synthesized and could be used as a probe for early detection of leprosy.

  通过使用线性合成路​​线有效地合成了具有对氨基乙基苯酚基团的PGL-1表位1。开发了一种有效合成含有鼠李糖环的寡糖的方法。化学方法具有灵活性，可用于合成其他PGL抗原。合成了生物素化的PGL-1抗原23，可用作早期检测麻风病的探针。
• Homogeneous competitive assay of ligand affinities based on quenching fluorescence of tyrosine/tryptophan residues in a protein via Főrster-resonance-energy-transfer
  作者：Yanling Xie、Xiaolan Yang、Jun Pu、Yunsheng Zhao、Ying Zhang、Guoming Xie、Jun Zheng、Huidong Yuan、Fei Liao

  DOI：10.1016/j.saa.2010.08.021

  日期：2010.11

  A new homogeneous competitive assay of ligand affinities was proposed based on quenching the fluorescence of tryptophan/tyrosine residues in a protein via Főrster-resonance-energy-transfer using a fluorescent reference ligand as the acceptor. Under excitation around 280 nm, the fluorescence of a protein or a bound acceptor was monitored upon competitive binding against a nonfluorescent candidate ligand

  基于荧光参考配体作为受体，通过弗斯特共振能量转移淬灭蛋白质中色氨酸/酪氨酸残基的荧光，提出了一种配体亲和力的新的均质竞争测定法。在280nm附近的激发下，在与非荧光候选配体竞争结合时监测蛋白质或结合的受体的荧光。讨论了用任一荧光信号推导受体结合率的化学计量学；离解常数（K d从其取代受体的50％结合的浓度计算非荧光候选配体的）。N-生物素-N'-（1-萘基）-乙二胺（BNEDA）和N-生物素-N'-丹酰基-乙二胺（BDEDA）被用作链霉亲和素的参考配体和受体，以测试这种新的均相竞争性测定。受体与链霉亲和素结合后，链霉亲和素荧光在340 nm处猝灭，BNEDA在430 nm处或BDEDA在525 nm处具有特征荧光。BNEDA和BDEDA的K d是通过竞争性结合生物素获得的。通过定量BNEDA荧光K d通过使用BNEDA或BDEDA作为受体对链霉亲和素荧光进行定量，每种测试的非荧光生物素衍生
• Caspase-3 controlled assembly of nanoparticles for fluorescence turn on
  作者：Chun-yan Cao、Yue Chen、Fang-zhou Wu、Yun Deng、Gao-lin Liang

  DOI：10.1039/c1cc14112k

  日期：——

  A caspase-3 controlled condensation was applied to self-assemble biotinylated nanoparticles for capturing FITC-labelled streptavidin and subsequently turning on the fluorescence signal.

  应用 caspase-3 控制的浓缩来自组装生物素化纳米粒子，以捕获 FITC 标记的链霉亲和素并随后打开荧光信号。
• Selective Covalent Targeting of Pyruvate Kinase M2 Using Arsenous Warheads
  作者：Jingyao Wang、Shaoqing Zhou、Yan Cheng、Lin Cheng、Ying Qin、Zhenfeng Zhang、Aiwei Bi、Huaijiang Xiang、Xinheng He、Xiaoxu Tian、Wenbin Liu、Jian Zhang、Chao Peng、Zhengjiang Zhu、Min Huang、Ying Li、Guanglei Zhuang、Li Tan

  DOI：10.1021/acs.jmedchem.2c01563

  日期：2023.2.23

  in covalent targeted inhibitors in drug discovery against previously “undruggable” sites and targets. These molecules typically feature an electrophilic warhead that reacts with nucleophilic groups of protein residues, most notably the thiol group of cysteines. One main challenge in the field is to develop versatile utilizable warheads. Here, we characterize the unique features of novel arsenous warheads

  在针对以前“不可药化”的位点和靶标的药物发现中，人们对共价靶向抑制剂的兴趣越来越大。这些分子通常具有与蛋白质残基的亲核基团反应的亲电子弹头，最显着的是半胱氨酸的硫醇基团。该领域的一项主要挑战是开发多功能的可利用弹头。在这里，我们描述了新型砷弹头以可逆方式与硫醇物种反应的独特特征，并进一步证明有机砷探针可以通过开发选择性和有效的丙酮酸激酶 M2 (PKM2) 抑制剂来化学调节特定分子靶标。我们表明化合物24是 PKM2 及其口服生物可利用前药25的共价变构抑制剂在体外和体内有效抑制 PKM2 依赖性肿瘤生长。我们的结果介绍了25及其衍生物作为有用的药理学工具，并提供了使用砷弹头靶向蛋白质半胱氨酸组的一般路线图。