15-生物素-氨基-4,7,10,13-二氧杂壬酸N-羟基琥珀酰亚胺 | 459426-22-3

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 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: 15-生物素-氨基-4,7,10,13-二氧杂壬酸N-羟基琥珀酰亚胺
• 中文别名: 21-[(3AS,4S,6AR)-六氢-2-氧代-1H-噻吩并[3,4-D]咪唑-4-基]-17-氧代-4,7,10,13-四氧杂-16-氮杂二十一碳酸 2,5-二氧代-1-吡咯烷基酯
• 英文名称: NHS-PEG₄-Biotin
• 英文别名: biotin-PEG₄-NHS；biotin-PEG4-NHS ester；(2,5-dioxopyrrolidin-1-yl) 3-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoate
• CAS: 459426-22-3
• 化学式: C₂₅H₄₀N₄O₁₀S
• 分子量: 588.679
• InChiKey: DTLVBHCSSNJCMJ-JXQFQVJHSA-N

物化性质

• 密度：
  1.33±0.1 g/cm3(Predicted)
• 溶解度：
  溶于DMSO、DMF、DCM

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  40
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  196
• 氢给体数：
  3
• 氢受体数：
  11

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  2-8℃

制备方法与用途

Biotin-PEG4-NHS酯是一种生物素标记的PROTAC连接子，属于PEG类化合物，可用于合成PROTAC分子。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  21-[(3aS,4S,6aR)-六氢-2-氧代-1H-噻吩并[3,4-d]咪唑-4-基]-17-氧代-4,7,10,13-四氧杂-16-氮杂二十一烷酸	17-oxo-21-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-4,7,10,13-tetraoxa-16-azahenicosan-1-oic acid	721431-18-1	C21H37N3O8S	491.606

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(2-chlorophenyl)methyl N-[4-[(2R,5S,8S,11S,14R)-5-[4-[3-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]butyl]-11,14-dibenzyl-13-methyl-8-(2-methylpropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]butyl]carbamate	1374429-86-3	C66H95ClN10O14S	1320.06
  ——	(2-chlorophenyl)methyl N-[4-[(2R,5S,8S,11S,14R)-8-[4-[3-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]butyl]-11,14-dibenzyl-13-methyl-3,6,9,12,15-pentaoxo-5-propan-2-yl-1,4,7,10,13-pentazacyclopentadec-2-yl]butyl]carbamate	1374429-80-7	C65H93ClN10O14S	1306.03
  ——	N-(2-(2-(2-(2-(3-(2-(4-(5-(4-fluorophenyl)-4-(pyridin-4-yl)-1H-pyrrol-2-yl)piperidin-1-yl)ethylamino)-3-oxopropoxy)ethoxy)ethoxy)ethoxy)ethyl)-5-((3aS,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide	1426406-59-8	C43H60FN7O7S	838.057

反应信息

• 作为反应物：
  描述：

  15-生物素-氨基-4,7,10,13-二氧杂壬酸N-羟基琥珀酰亚胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 30.0h， 生成 N-(4-((6-azidohexyloxy)diphenylsilyloxy)butyl)-1-(5-((3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl)-pentanamido)-3,6,9,12-tetraoxapentadecan-15-amide
  参考文献：
  名称：

  Cleavable Biotin Probes for Labeling of Biomolecules via Azide−Alkyne Cycloaddition

  摘要：

  The azide-alkyne cycloaddition provides a powerful tool for bio-orthogonal labeling of proteins, nucleic acids, glycans, and lipids. In some labeling experiments, e.g., in proteomic studies involving affinity purification and mass spectrometry, it is convenient to use cleavable probes that allow release of labeled biomolecules under mild conditions. Five cleavable biotin probes are described for use in labeling of proteins and other biomolecules via azide-alkyne cycloaddition. Subsequent to conjugation with metabolically labeled protein, these probes are subject to cleavage with either 50 mM Na2S2O4, 2% HOCH2CH2SH, 10% HCO2H, 95% CF3CO2H, or irradiation at 365 nm. Most strikingly, a probe constructed around a dialkoxydiphenylsilane (DADPS) linker was found to be cleaved efficiently when treated with 10% HCO2H for 0.5 h. A model green fluorescent protein was used to demonstrate that the DADPS probe undergoes highly selective conjugation and leaves a small (143 Da) mass tag on the labeled protein after cleavage. These features make the DADPS probe especially attractive for use in biomolecular labeling and proteomic studies.

  DOI：

  10.1021/ja1083909
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 21-[(3aS,4S,6aR)-六氢-2-氧代-1H-噻吩并[3,4-d]咪唑-4-基]-17-氧代-4,7,10,13-四氧杂-16-氮杂二十一烷酸 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 15-生物素-氨基-4,7,10,13-二氧杂壬酸N-羟基琥珀酰亚胺
  参考文献：
  名称：

  Endocytosis and Intracellular Dissociation Rates of Human Insulin–Insulin Receptor Complexes by Quantum Dots in Living Cells

  摘要：

  Insulin signaling is involved in glucose metabolism, cellular growth, and differentiation. Its function is altered in diabetes and many cancer types. Insulin binding to insulin receptor (IR) triggers diverse signaling pathways. However, signal transduction by IR is not mediated exclusively at the cell surface. Activated ligand-receptor complexes are internalized into endosomes from which the IR recruits adapters acting on substrates that are distinct from those accessible at the membrane. We report the biotinylation of human-recombinant insulin (rhIns) specifically at the position 29 of the B chain. We combined visible fluorescent proteins fused to IR and biotinylated rhIns conjugated with streptavidin-quantum dots to perform extended, quantitative experiments in real time. Modified thins bound to the IR and conjugated with the quantum dots was internalized with a rate constant (k) of 0.009 min(-1). Dissociation of insulin-IR complex in endocytosed vesicles occurred with k = 0.006 min(-1).

  DOI：

  10.1021/bc300526d

文献信息

• [EN] ANTIBODY CONJUGATES COMPRISING TOLL-LIKE RECEPTOR AGONIST AND COMBINATION THERAPIES<br/>[FR] CONJUGUÉS D'ANTICORPS COMPRENANT UN AGONISTE DU RÉCEPTEUR DE TYPE TOLL ET POLYTHÉRAPIES
  申请人：NOVARTIS AG

  公开号：WO2018198091A1

  公开（公告）日：2018-11-01

  Provided herein are antibody conjugates comprising toll-like receptor agonists and the use of such conjugates for the treatment of cancer. In some embodiments, the conjugates comprise anti-HER2 antibodies. In some embodiments, the conjugates are used in combination with a second therapeutic agent.

  本文提供了包含Toll样受体激动剂的抗体偶联物，以及利用这些偶联物治疗癌症的用途。在某些实施例中，这些偶联物包括抗HER2抗体。在某些实施例中，这些偶联物与第二治疗剂联合使用。
• [EN] ANTIBODY CONJUGATES COMPRISING TOLL-LIKE RECEPTOR AGONIST<br/>[FR] CONJUGUÉS D'ANTICORPS COMPRENANT UN AGONISTE DU RÉCEPTEUR DE TYPE TOLL
  申请人：NOVARTIS AG

  公开号：WO2017072662A1

  公开（公告）日：2017-05-04

  Provided herein are antibody conjugates comprising toll-like receptor agonists and the use of such conjugates for the treatment of cancer. In some embodiments, the conjugates comprise anti-HER2 antibodies.

  本文提供了包含Toll样受体激动剂的抗体偶联物，以及利用这些偶联物治疗癌症的用途。在某些实施例中，这些偶联物包括抗HER2抗体。
• Simultaneous Arming and Structure/Activity Studies of Natural Products Employing O−H Insertions:  An Expedient and Versatile Strategy for Natural Products-Based Chemical Genetics
  作者：Satyamaheshwar Peddibhotla、Yongjun Dang、Jun O. Liu、Daniel Romo

  DOI：10.1021/ja0733686

  日期：2007.10.1

  diverse set of natural products, and general guidelines for predicting chemosite selectivity were formulated. A subsequent Sharpless-Hüisgen [3 + 2] cycloaddition reaction with the appended alkyne allows for attachment of a variety of reporter tags. Using this strategy, we synthesized a novel FK506-biotin conjugate that enabled pull-down of the entire "immunosuppressive complex" including FKBP12, calcineurins

  确定“可成药”靶点是后基因组时代的直接机遇和挑战。天然产物是基础细胞研究的持久工具，也是鉴定医学相关蛋白质靶标的先导。然而，它们在这些研究中的使用往往受到数量有限和缺乏选择性和温和的单官能化反应的阻碍。开发选择性方法可以同时为天然产物配备反应基团，以便随后与报告标记结合并提供重要的构效关系 (SAR) 信息，只需了解天然产物中存在的官能团，就可以显着降低生物活性天然产物分离和目标鉴定之间的时间。在此处，我们报告了这样一种策略，该策略能够对含醇的天然产物进行同步武装和 SAR 研究，包括化学和位点选择性（“化学位点”选择性）和位点非选择性 OH 插入反应，与来自炔基重氮乙酸酯的铑类碳化物反应。该策略应用于多种天然产物，并制定了预测化学位点选择性的一般指南。随后的 Sharpless-Hüisgen [3 + 2] 环加成反应与附加的炔烃允许连接各种报告标签。使用这种策略，我们合成了一种新型
• Synthesis of biotinylated keratan sulfate repeating disaccharides
  作者：Naoko Takeda、Jun-ichi Tamura

  DOI：10.1080/09168451.2014.877834

  日期：2014.1.2

  We synthesized four types of keratan and keratan sulfate repeating disaccharides containing non-sulfate, Galβ1-4GlcNAcβ, and three types of sulfates, Gal6Sβ1-4GlcNAcβ, Galβ1-4GlcNAc6Sβ, and Gal6Sβ1-4GlcNAc6Sβ in an efficient and stereo-controlled manner. These disaccharides were conjugated with biotin via a hydrophilic linker at the reducing terminal.

  我们以一种高效和立体控制的方式合成了四种类型的角质蛋白和角质蛋白硫酸盐重复二糖，其中包含非硫酸盐的Galβ1-4GlcNAcβ和三种硫酸盐，Gal6Sβ1-4GlcNAcβ、Galβ1-4GlcNAc6Sβ和Gal6Sβ1-4GlcNAc6Sβ。这些二糖通过一个亲水连接剂与生物素结合在还原末端。
• Synthesis of chondroitin sulfate CC and DD tetrasaccharides and interactions with 2H6 and LY111
  作者：Kenya Matsushita、Tomomi Nakata、Naoko Takeda-Okuda、Satomi Nadanaka、Hiroshi Kitagawa、Jun-ichi Tamura

  DOI：10.1016/j.bmc.2018.01.011

  日期：2018.3

  We synthesized the biotinylated chondroitin sulfate tetrasaccharides CS-CC [-3)βGalNAc6S(1–4)βGlcA(1-]2 and CS-DD [-3)βGalNAc6S(1–4)βGlcA2S(1-]2 which possess sulfate groups at O-6 of GalNAc and an additional sulfate group at O-2 of GlcA, respectively. We also analyzed interactions among CS-CC and CS-DD and the antibodies 2H6 and LY111, both of which are known to bind with CS-A, while CS-DD was shown

  我们合成了具有硫酸盐基团的生物素化硫酸软骨素四糖CS-CC [-3]βGalNAc6S（1-4）βGlcA（1-] 2和CS-DD [-3）βGalNAc6S（1-4）βGlcA2S（1-] 2在Ô在-6的GalNAc和附加硫酸基的ö -2中，GlcA的分别。我们还分析中CS-CC和CS-DD和抗体2H6和LY111，这两者都是已知结合与CS-A相互作用，而CS-DD首次显示可与两种抗体结合。