5-(2-oxohexahydrothieno[3,4-d]imidazol-4-yl)pentanoic acid (2-{2-[5-(2-oxohexahydrothieno[3,4-d]imidazol-4-yl)pentanoylamino]ethyldisulfanyl}ethyl)amide | 135075-40-0

• 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: 5-(2-oxohexahydrothieno[3,4-d]imidazol-4-yl)pentanoic acid (2-{2-[5-(2-oxohexahydrothieno[3,4-d]imidazol-4-yl)pentanoylamino]ethyldisulfanyl}ethyl)amide
• 英文别名: N,N'-(disulfanediylbis(ethane-2,1-diyl))bis(5-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide)；bis((2-N-D-biotin)ethylamide)disulfide；5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethyldisulfanyl]ethyl]pentanamide
• CAS: 135075-40-0
• 化学式: C₂₄H₄₀N₆O₄S₄
• 分子量: 604.883
• InChiKey: HOGVHKJVLPASTN-CSOYKPOESA-N

物化性质

• 沸点：
  1023.5±65.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  38
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  242
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-(2-oxohexahydrothieno[3,4-d]imidazol-4-yl)pentanoic acid (2-{2-[5-(2-oxohexahydrothieno[3,4-d]imidazol-4-yl)pentanoylamino]ethyldisulfanyl}ethyl)amide 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 1,4-二巯基-2,3-丁二醇 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 3-(2-thioethyl-D-biotin amide)-4-formyl-2,2,5,5-tetramethyl-1H-pyrrol-1-yloxyl
  参考文献：
  名称：

  用于表面上配体识别的双功能自旋标签。

  摘要：

  原位监测生物分子识别，尤其是在表面，仍然是一项重大的技术挑战。用氮氧化物自旋标记的生物分子的电子顺磁共振（EPR）可以提供对这些过程的独特敏感和选择性见解，但是需要新的自旋标记策略。报道了具有两个具有正交反应性的连接点的溴丙烯醛自旋标记（BASL）的合成和研究。甘露糖和生物素配体通过自旋标记偶联到羧基官能化的金纳米颗粒水溶液的第一个例子。获得自旋标记的配体在溶液中游离并附着在纳米颗粒上的EPR光谱。标记被甘露糖结合凝集素，Con A和生物素结合蛋白抗生物素蛋白过氧化物酶识别。

  DOI：

  10.1002/anie.201703929
• 作为产物：
  描述：

  D-生物素 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 5-(2-oxohexahydrothieno[3,4-d]imidazol-4-yl)pentanoic acid (2-{2-[5-(2-oxohexahydrothieno[3,4-d]imidazol-4-yl)pentanoylamino]ethyldisulfanyl}ethyl)amide
  参考文献：
  名称：

  醛介导的生物共轭作用，通过原位产生的乙叉。

  摘要：

  已经为体外和细胞应用开发了一种技术上简单的快速，高产和位点选择性生物缀合方法。该方法涉及在生理条件下通过4-硝基苯酚催化生成马来酰亚胺基，然后与附加醛的生物分子进行维蒂希反应。

  DOI：

  10.1039/c9cc07443k

文献信息

• Intracellular Delivery of Functional Proteins and Native Drugs by Cell-Penetrating Poly(disulfide)s
  作者：Jiaqi Fu、Changmin Yu、Lin Li、Shao Q. Yao

  DOI：10.1021/jacs.5b08130

  日期：2015.9.23

  discovery. We report herein the development of novel methods for intracellular delivery of functional proteins (including antibodies) and native small-molecule drugs by making use of cell-penetrating poly(disulfide)s (CPDs). CPDs were recently shown to be rapidly taken up by mammalian cells in endocytosis-independent pathways, but their applications for delivery of proteins and native small-molecule

  将生物活性化合物有效递送到细胞中是药物发现的主要挑战。我们在此报告了利用细胞穿透性聚（二硫化物）（CPD）在细胞内递送功能性蛋白质（包括抗体）和天然小分子药物的新方法的发展。CPDs 最近被证明在不依赖于内吞作用的途径中被哺乳动物细胞迅速吸收，但它们在递送蛋白质和天然小分子药物方面的应用尚未得到证实。借助我们新开发的 CPD 辅助方法，使用预先合成的 CPD 在水性条件下分两步在几分钟内快速和“生物正交”装载货物。得到的 CPD-货物结合物立即用于后续的细胞递送研究。凭借这些方法的多功能性和灵活性，我们进一步表明它们可用于以最少的化学和遗传操作立即交付各种功能性货物。这些 CPD 及其载货偶联物的最小细胞毒性进一步突出了这种新的细胞转导方法相对于其他现有策略的独特优势，并确保我们的整个传递协议与后续的活细胞实验和生物学研究兼容。
• Photoinduced Addition of Glycosyl Thiols to Alkynyl Peptides: Use of Free-Radical Thiol−Yne Coupling for Post-Translational Double-Glycosylation of Peptides
  作者：Mauro Lo Conte、Salvatore Pacifico、Angela Chambery、Alberto Marra、Alessandro Dondoni

  DOI：10.1021/jo1008178

  日期：2010.7.2

  peptides has been carried out by a one-pot two-step sequence comprising selective S-propargylation followed by photoinduced (λ max 365 nm) free-radical hydrothiolation with glycosyl thiols. Conditions were established for the sequential introduction of two different thiol residues such as a glycosyl and a biotinyl derivative.

  含半胱氨酸的肽的双糖基化已经通过一锅两步的顺序进行，该步骤包括选择性的S-炔丙基化，然后用糖基硫醇进行光诱导的（λmax 365 nm）自由基氢硫醇化。为依次引入两个不同的硫醇残基（例如糖基和生物素基衍生物）建立了条件。
• Advanced Aqueous-Phase Phosphoramidation Reactions for Effectively Synthesizing Peptide–Oligonucleotide Conjugates Trafficked into a Human Cell Line
  作者：Tzu-Pin Wang、Ni Chien Ko、Yu-Chih Su、Eng-Chi Wang、Scott Severance、Chi-Ching Hwang、Ying Ting Shih、Min Hui Wu、Yen-Hsu Chen

  DOI：10.1021/bc300444y

  日期：2012.12.19

  Peptide-oligonucleotide conjugates (POCs) have held promise as effective therapeutic agents in treating microbial infections and human genetic diseases including cancers. In clinical applications, POCs are especially useful to circumvent cellular delivery and specificity problems of oligonucleotides. We previously reported that nucleic acid phosphoramidation reactions performed in aqueous solutions have the potential for facile POC synthesis. Here, we carried out further studies to significantly improve aqueous-phase two-step phosphoramidation reaction yield. Optimized reactions were employed to effectively synthesize POCs for delivery into human A549 cells. We achieved optimization of aqueous-phase two-step phosphoramidation reaction and improved reaction yield by (1) determining appropriate co-solutes and co-solute concentrations to acquire higher reaction yields, (2) exploring a different nucleophilicity of imidazole and its derivatives to stabilize essential nucleic acid phosphorimidazolide intermediates prior to POC formation, and (3) enhancing POC synthesis by increasing reactant nucleophilicity. The advanced two-step phosphoramidation reaction was exploited to effectively conjugate a well-studied cell penetrating peptide, the Tat(48-57) peptide, with oligonucleotides, bridged by either no linkers or a disulfide-containing linker, to have the corresponding POC yields of 47-75%. Phosphoramidation-synthesized POCs showed no cytotoxicity to human A549 cells at studied POC concentrations after 24 h inoculation and were successfully trafficked into the human A549 cell line as demonstrated by flow cytometry, fluorescent microscopy, and confocal laser scanning microscopy study. The current report provides insight into aqueous-phase phosphoramidation reactions, the knowledge of which was used to develop effective strategies for synthesizing POCs with crucial applications including therapeutic agents for medicine.
• Smart tools and orthogonal click-like reactions onto small unilamellar vesicles
  作者：Christophe Salomé、Maria Vittoria Spanedda、Benoit Hilbold、Etienne Berner、Béatrice Heurtault、Sylvie Fournel、Benoit Frisch、Line Bourel-Bonnet

  DOI：10.1016/j.chemphyslip.2015.03.004

  日期：2015.5

  Click-based reactions were conducted at the surface of small unilamellar vesicles (SUVs) to provide onto-vesicle chemistry with efficient innovative ready-for-use tools. For that purpose, four amphiphilic molecules were designed to insert into bilayers while presenting a reactive functional head. In this manner, a dioleylglycero-ethoxy-ethoxy-ethoxy-ethanamine (DOG-PEG(4)-NH2) was chosen as a common platform while the reactive amine head was converted into several electrophilic functions. Thus, two dioleylglycerol-based cyclooctyne anchors were prepared: cyclooct-1-yn-3-glycolic acid-based anchor (DOG-COA) and 1-fluorocyclooct-2-ynecarboxylic acid-based anchor (DOG-FCOA). The last one differed from the first one in that a fluorine atom reinforces the electrophilic properties of the unsaturated bond. In addition, a third dioleylglycerol-based triphenylphosphine (DOG-PPh3) was synthesized for the first time. These three innovative amphiphilic anchors were designed to react with any azide-based biomolecule following copper-free Huisgen 1,4-cycloaddition and Staudinger ligation, respectively. A fourth anchor bearing a 3,4-dibromomaleimide ring (DOG-DBM) was also unprecedentedly synthesized, to be further substituted by two thiols. Model reactions conducted in solution with either model biotinyl azide or model biotinyl disulfide gave good to total conversions and excellent isolated yields. The four new anchors were inserted into SUVs whose formula is classically used in in vivo biology. Stability and surface overall electrostatic charge were in the expected range and constant over the study. Then, the functionalized liposomes were ligated to biotin-based reagents and the experimental conditions were finely tuned to optimize the conversion. The biotinyl liposomes were demonstrated functional and totally accessible in an affinity test based on biotin scaffold quantification. Finally, DOG-FCOA's reactivity was confronted to that of DOG-DBM in a 'one-pot' orthogonal reaction. (Biotin-S)(2) and TAMRA-N-3 (tetramethylcarboxyrhodamine azide) were successively conjugated to the liposome suspension in a successful manner. These data implement and reinforce the interest of bioorthogonal click-like reactions onto lipid nanoparticles. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
• Janus Au-mesoporous silica nanoparticles as electrochemical biorecognition-signaling system
  作者：Alfredo Sánchez、Paula Díez、Paloma Martínez-Ruíz、Reynaldo Villalonga、José M. Pingarrón

  DOI：10.1016/j.elecom.2013.02.008

  日期：2013.5

  Janus Au-mesoporous silica nanoparticles were used as scaffolds to design an integrated electrochemical biorecognition-signaling system. A proof of concept of this strategy, based on the face-selective functionalization of the anisotropic colloid, involves the covalent immobilization of horseradish peroxidase on the mesoporous silica face as enzymatic signaling element, as well as the modification of the Au face with streptavidin and polyethylenglycol chains as biorecognition and solubilizing agents, respectively. The functionalized Janus nanoparticles were successful to recognize biotin on gold surfaces. (C) 2013 Elsevier B.V. All rights reserved.