N-碘代乙酸基-N-生物素己二胺 | 93285-75-7

• 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
• 中文名称: N-碘代乙酸基-N-生物素己二胺
• 中文别名: N-碘代乙酰基-N'-生物素基-1,6-己二胺
• 英文名称: N-iodoacetyl-N-biotinylhexylenediamine
• 英文别名: iodoacetyl-LC-biotin；N-Biotinyl-N'-(iodoacetyl)-1,6-hexanediamine；5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[6-[(2-iodoacetyl)amino]hexyl]pentanamide
• CAS: 93285-75-7
• 化学式: C₁₈H₃₁IN₄O₃S
• 分子量: 510.44
• InChiKey: DNXDWMHPTVQBIP-ZQIUZPCESA-N

物化性质

• 沸点：
  793.7±60.0 °C(Predicted)
• 密度：
  1.414±0.06 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  DMSO 中≥51 mg/mL，温和加热；不溶于乙醇；不溶于水

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  27
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P362,P403+P233,P501
• 危险性描述：
  H315,H319,H335

制备方法与用途

生物活性

Iodoacetyl-LC-biotin 是一种生物素化的亲电子探针，可用于研究蛋白质共价结合至亚细胞蛋白质组的范围和特征。

体外研究

Iodoacetyl-LC-biotin (IAB) (50-200 μM; 6-24 h) increases LDH leakage in HEK293 cells in a time- and dose-dependant manner.
IAB (50-200 µM; 24 h) causes the release of cytochrome c from the mitochondria to the cytosol in HEK293 cells.

反应信息

• 作为反应物：
  描述：

  N-碘代乙酸基-N-生物素己二胺 、 10-羟基喜树碱 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(6-(2-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)acetamido)hexyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide
  参考文献：
  名称：

  Identification of C10 biotinylated camptothecin (CPT-10-B) binding peptides using T7 phage display screen on a QCM device

  摘要：

  A peptide sequence that can bind to camptothecin (CPT), a natural cytotoxic compound, was screened for using a T7 phage display system combined with a cuvette type quartz crystal microbalance (QCM) device. In this screen, after only 10 min of monitoring of the interaction between injected T7 phage pool with immobilized C10 biotinylated CPT (CPT-10-B) on a gold electrode surface, six different kinds of phage (A-F) were identified as judged by the size of PCR product on agarose gel electrophoresis. Injection of each single phage (A-E) pool individually caused a frequency decrease, suggesting interaction with the immobilized CPT-10-B. In addition, the peptide sequence displayed on phages A-C is consistent with chemical and biological studies of the interaction of CPTs with topoisomerase I (TopI), human E prostanoid receptor third cytoplasmic polypeptide, and a series of esterases. The efficacy of T7 phage display screening for small molecules on QCM devices, target discovery from primary peptide sequence, and application of this strategy to various drug-like small molecules are discussed. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.09.002

文献信息

• Chloroquine combination drugs and methods for their synthesis
  申请人：Kosak M. Kenneth

  公开号：US20070060499A1

  公开（公告）日：2007-03-15

  This invention discloses compositions of chloroquine-coupled active agents, including methods for their preparation. The prior art has shown that chloroquines given as free drug in high enough concentration, enhances the release of various agents from cellular endosomes into the cytoplasm. The purpose of these compositions is to provide a controlled amount of chloroquine at the same site where the active agent is delivered, thereby reducing the overall dosage needed. The compositions comprise a chloroquine substance coupled to an active agent directly or through a variety of pharmaceutical carrier substances. The carrier substances include polysaccharides, synthetic polymers, proteins, micelles and other substances for carrying and releasing the chloroquine compositions in the body for therapeutic effect. The compositions can also include a biocleavable linkage for carrying and releasing active agents for therapeutic or other medical uses. The invention also discloses carrier compositions that are coupled to targeting molecules for targeting the delivery of chloroquine substances and active agents to their site of action.

  这项发明揭示了氯喹偶联活性药剂的组合物，包括其制备方法。先前的技术已经表明，以足够高浓度给予氯喹作为游离药物，可以增强细胞内体内各种药剂从细胞内体释放到细胞质中。这些组合物的目的是在传递活性药剂的相同部位提供受控量的氯喹，从而减少所需的总剂量。这些组合物包括将氯喹物质直接或通过各种药用载体物质偶联到活性药剂。载体物质包括多糖、合成聚合物、蛋白质、胶束和其他用于在体内携带和释放氯喹组合物以产生治疗效果的物质。这些组合物还可以包括用于携带和释放活性药剂以用于治疗或其他医疗用途的生物可降解连接。该发明还揭示了与靶向分子偶联的载体组合物，用于将氯喹物质和活性药剂定位传递到它们的作用部位。
• A Screening of a Library of T7 Phage-Displayed Peptide Identifies E2F-4 as an Etoposide-Binding Protein
  作者：Mihoko Takami、Yoichi Takakusagi、Kouji Kuramochi、Senko Tsukuda、Satoko Aoki、Kengo Morohashi、Keisuke Ohta、Susumu Kobayashi、Kengo Sakaguchi、Fumio Sugawara

  DOI：10.3390/molecules16054278

  日期：——

  Etoposide (VP-16) is an anti-tumor compound that targets topoisomerase II (top II). In this study, we have identified an alternative binding protein of etoposide by screening a library of T7 phage-displayed peptides. After four rounds of selection using a biotinylated etoposide derivative immobilized on a streptavidin-coated plate, T7 phage particles that display a 16-mer peptide NSSASSRGNSSSNSVY (ETBP16) or a 10-mer NSLRKYSKLK (ETBP10) were enriched with the ratio of 40 or 11 out of the 69 clones, respectively. Binding of etoposide to these peptides was confirmed by surface plasmon resonance (SPR) analysis, which showed ETBP16 and ETBP10 to have a kinetic constant of 4.85 × 10−5 M or 6.45 × 10−5 M, respectively. ETBP16 displays similarity with the ser-rich domain in E2F-4, a transcription factor in cell cycle-regulated genes, suggesting that etoposide might interact with E2F-4 via this domain. SPR analysis confirmed the specific binding of etoposide to recombinant E2F-4 is in the order of 10−5 M. Furthermore, etoposide was shown to inhibit luciferase reporter gene expression mediated by the heterodimeric E2F-4/DP complex. Taken together, our results suggest that etoposide directly binds to E2F-4 and inhibits subsequent gene transcription mediated by heterodimeric E2F-4/DP complexes in the nucleus.

  依托泊苷（VP-16）是一种针对拓扑异构酶 II（top II）的抗肿瘤化合物。在这项研究中，我们通过筛选 T7 噬菌体显示的肽库，发现了依托泊苷的替代结合蛋白。使用固定在链霉亲和素涂层平板上的生物素化依托泊苷衍生物进行四轮筛选后，在 69 个克隆中，显示 16 个单链肽 NSSASSRGNSSSNSVY（ETBP16）或 10 个单链肽 NSLRKYSKLK（ETBP10）的 T7 噬菌体颗粒分别富集了 40 或 11 个。表面等离子体共振（SPR）分析表明，ETBP16 和 ETBP10 的动力学常数分别为 4.85 × 10-5 M 或 6.45 × 10-5 M。ETBP16与细胞周期调控基因转录因子E2F-4中的富丝氨酸结构域相似，这表明依托泊苷可能通过该结构域与E2F-4相互作用。SPR 分析证实，依托泊苷与重组 E2F-4 的特异性结合为 10-5 M。综上所述，我们的研究结果表明，依托泊苷能直接与 E2F-4 结合，并抑制细胞核中由异源二聚体 E2F-4/DP 复合物介导的后续基因转录。
• Chloroquine coupled nucleic acids and methods for their synthesis
  申请人：Kosak M. Kenneth

  公开号：US20060040879A1

  公开（公告）日：2006-02-23

  This invention discloses compositions and methods for preparing chloroquine-coupled nucleic acid compositions. The prior art has shown that chloroquines given as free drug in high enough concentration, enhances the release of various agents from cellular endosomes into the cytoplasm. The purpose of these compositions is to provide a controlled amount of chloroquine at the same site where the nucleic acid needs to be released, thereby reducing the overall dosage needed. The compositions comprise a chloroquine substance coupled to a nucleic acid directly or through a variety of pharmaceutical carrier substances. The carrier substances include polysaccharides, synthetic polymers, proteins, micelles and other substances for carrying and releasing the chloroquine compositions in the body for therapeutic effect. The compositions can also include a biocleavable linkage for carrying and releasing nucleic acids for therapeutic or other medical uses. The invention also discloses nucleic acid carrier compositions that are coupled to targeting molecules for targeting the delivery of nucleic acids to their site of action.

  本发明披露了制备氯喹偶联核酸组合物的组成和方法。先前的研究表明，以足够高的浓度给予氯喹作为自由药物，可以增强细胞内体内各种物质从内体泡中释放到细胞质中。这些组合物的目的是在核酸需要释放的同一位置提供受控量的氯喹，从而降低所需的总剂量。该组合物包括直接或通过各种药物载体物质偶联的氯喹物质和核酸。载体物质包括多糖、合成聚合物、蛋白质、胶束和其他用于在体内携带和释放氯喹组合物以达到治疗效果的物质。该组合物还可以包括生物可降解连接来携带和释放用于治疗或其他医疗用途的核酸。本发明还披露了偶联到靶向分子的核酸载体组合物，用于将核酸传递到其作用位置。
• Production of Conjugates
  申请人：Gee Nicholas

  公开号：US20100184184A1

  公开（公告）日：2010-07-22

  Disclosed is a method for indirectly coupling a small molecule ligand to a molecule to be labelled with the ligand, the method comprising the step of: contacting a scaffold molecule, to which is attached at least one small molecule ligand, with the molecule to be labelled, the scaffold molecule having at least one group which is reactive towards a receiver moiety present or formed in situ on the molecule to be labelled, so as to forma bond between the scaffold molecule and the molecule to be labelled, thereby indirectly coupling the small molecule ligand to the molecule to be labelled.

  公开了一种间接耦合小分子配体到待标记分子的方法，该方法包括以下步骤：将至少一个小分子配体附着在支架分子上，将支架分子与待标记分子接触，支架分子具有至少一个对待标记分子上存在或原位形成的接收者基团具有反应性的基团，从而在支架分子和待标记分子之间形成键，从而间接将小分子配体耦合到待标记分子上。
• Production of conjugates
  申请人：Gee Nicholas

  公开号：US09176125B2

  公开（公告）日：2015-11-03

  Disclosed is a method for indirectly coupling a small molecule ligand to a molecule to be labelled with the ligand, the method comprising the step of: contacting a scaffold molecule, to which is attached at least one small molecule ligand, with the molecule to be labelled, the scaffold molecule having at least one group which is reactive towards a receiver moiety present or formed in situ on the molecule to be labelled, so as to forma bond between the scaffold molecule and the molecule to be labelled, thereby indirectly coupling the small molecule ligand to the molecule to be labelled.

  本发明公开了一种间接耦合小分子配体到待标记分子的方法，该方法包括以下步骤：将至少一个小分子配体连接到支架分子上，使之与待标记分子接触，支架分子具有至少一个可以与待标记分子上的接收体基团反应的基团，从而在支架分子和待标记分子之间形成键，从而间接耦合小分子配体到待标记分子。