N-cholesteryl-2-nitrobenzenesulfonamide | 390762-93-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: N-cholesteryl-2-nitrobenzenesulfonamide
• 英文别名: N-[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]-2-nitrobenzenesulfonamide
• CAS: 390762-93-3
• 化学式: C₃₃H₅₀N₂O₄S
• 分子量: 570.837
• InChiKey: LRNMLVYBTKYMTH-ACBDEFBISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.7
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-cholesteryl-2-nitrobenzenesulfonamide 在 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 27.0h， 生成 3-Amino-N-{3-[[(3S,8S,9S,10R,13R,14S,17R)-17-((R)-1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]-(2-nitro-benzenesulfonyl)-amino]-propyl}-propionamide
  参考文献：
  名称：

  Synthetic Mimics of Small Mammalian Cell Surface Receptors

  摘要：

  Receptors on the surface of mammalian cells promote the uptake of cell-impermeable ligands by receptor-mediated endocytosis. To mimic this process, we synthesized small molecules designed to project anti-dinitrophenyl antibody-binding motifs from the surface of living Jurkat lymphocytes. These synthetic receptors comprise N-alkyl derivatives of 3beta-cholesterylamine as the plasma membrane anchor linked to 2,4-dinitrophenyl (DNP) and structurally similar fluorescent 7-nitrobenz-2-oxa-1,3-diazole (NBD) headgroups. Insertion of two beta-alanine subunits between a DNP derivative and 3beta-cholesterylamine yielded a receptor that avidly associates with cell surfaces (cellular t(1/2) similar to 20 h). When added to Jurkat cells at 10 muM, this receptor enhanced uptake of an anti-DNP IgG ligand by similar to200-fold in magnitude and similar to400-fold in rate within 4 h (ligand internalization t(1/2) similar to 95 min at 37 degreesC). This non-natural receptor mimics many natural receptors by dynamically cycling between plasma membranes and intracellular endosomes (recycling t(1/2) similar to 3 min), targeting of protein ligands to proposed cholesterol and sphingolipid-enriched lipid raft membrane microdomains, and delivery of protein ligands to late endosomes/lysosomes. Quantitative dithionite quenching of fluorescent extracellular NBD headgroups demonstrated that other 3beta-cholesterylamine derivatives bearing fewer beta-alanines in the linker region or N-acyl derivatives of 3beta-cholesterylamine were less effective receptors due to more extensive trafficking to internal membranes. Synthetic cell surface receptors have potential applications as cellular probes, tools for drug delivery, and methods to deplete therapeutically important extracellular ligands.

  DOI：

  10.1021/ja046663o
• 作为产物：
  描述：

  5-胆甾烯-3-酮 在 lithium aluminium tetrahydride 、 三(2-氯乙基)胺 、 L-Selectride 、 N,N-二异丙基乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醚 、 甲苯 、 苯 为溶剂， 反应 6.0h， 生成 N-cholesteryl-2-nitrobenzenesulfonamide
  参考文献：
  名称：

  Synthetic Mimics of Small Mammalian Cell Surface Receptors

  摘要：

  Receptors on the surface of mammalian cells promote the uptake of cell-impermeable ligands by receptor-mediated endocytosis. To mimic this process, we synthesized small molecules designed to project anti-dinitrophenyl antibody-binding motifs from the surface of living Jurkat lymphocytes. These synthetic receptors comprise N-alkyl derivatives of 3beta-cholesterylamine as the plasma membrane anchor linked to 2,4-dinitrophenyl (DNP) and structurally similar fluorescent 7-nitrobenz-2-oxa-1,3-diazole (NBD) headgroups. Insertion of two beta-alanine subunits between a DNP derivative and 3beta-cholesterylamine yielded a receptor that avidly associates with cell surfaces (cellular t(1/2) similar to 20 h). When added to Jurkat cells at 10 muM, this receptor enhanced uptake of an anti-DNP IgG ligand by similar to200-fold in magnitude and similar to400-fold in rate within 4 h (ligand internalization t(1/2) similar to 95 min at 37 degreesC). This non-natural receptor mimics many natural receptors by dynamically cycling between plasma membranes and intracellular endosomes (recycling t(1/2) similar to 3 min), targeting of protein ligands to proposed cholesterol and sphingolipid-enriched lipid raft membrane microdomains, and delivery of protein ligands to late endosomes/lysosomes. Quantitative dithionite quenching of fluorescent extracellular NBD headgroups demonstrated that other 3beta-cholesterylamine derivatives bearing fewer beta-alanines in the linker region or N-acyl derivatives of 3beta-cholesterylamine were less effective receptors due to more extensive trafficking to internal membranes. Synthetic cell surface receptors have potential applications as cellular probes, tools for drug delivery, and methods to deplete therapeutically important extracellular ligands.

  DOI：

  10.1021/ja046663o

文献信息

• Synthetic mimics of mammalian cell surface receptors: method and compositions
  申请人：Peterson R. Blake

  公开号：US20060229235A1

  公开（公告）日：2006-10-12

  The present invention relates to new synthetic receptors. More particularly, the present invention relates to the use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

  本发明涉及新的合成受体。更具体地，本发明涉及利用合成受体通过受体介导的内吞作用将蛋白质、肽、药物、前药、脂质、核酸、碳水化合物或小分子输送到靶细胞中。根据本发明，已设计了细胞表面受体的新型合成模拟物，并公开了其使用方法。
• Glycocalyx Engineering with a Recycling Glycopolymer that Increases Cell Survival In Vivo
  作者：Elliot C. Woods、Nathan A. Yee、Jeff Shen、Carolyn R. Bertozzi

  DOI：10.1002/anie.201508783

  日期：2015.12.21

  Strikingly, we found that cholesterylamine (CholA) anchored glycopolymers are internalized into vesicles that serve as depots for delivery back to the cell surface, allowing for the display of cell‐surface glycopolymers for at least ten days, even while the cells are dividing. As with native mucins, the cell‐surface display of CholA‐anchored glycopolymers influenced the focal adhesion distribution. Furthermore

  模拟细胞表面粘蛋白的合成糖聚合物已被用于阐明粘蛋白过度表达在癌症中的作用。然而，由于它们在数小时内内化，这些糖聚合物不能用于探测在较长时间尺度上发生的过程。在这项工作中，我们测试了一组含有各种脂质的糖聚合物，以确定那些持续存在于细胞膜上的糖聚合物。引人注目的是，我们发现胆固醇胺 (CholA) 锚定的糖聚合物被内化到囊泡中，这些囊泡作为贮库输送回细胞表面，即使在细胞分裂时，细胞表面的糖聚合物也可以展示至少 10 天。与天然粘蛋白一样，CholA 锚定的糖聚合物的细胞表面展示会影响粘着斑分布。此外，我们表明，这些模拟物提高了斑马鱼转移模型中非恶性细胞的存活率。因此，CholA 锚定的糖聚合物扩大了糖萼工程在糖生物学中的应用。
• Efficient Delivery of Streptavidin to Mammalian Cells:  Clathrin-Mediated Endocytosis Regulated by a Synthetic Ligand
  作者：Stephen L. Hussey、Blake R. Peterson

  DOI：10.1021/ja0258733

  日期：2002.6.1

  affected. Structurally related ligands bearing a shorter linker or substituting the protonated steroidal amine with an isosteric amide were ineffective molecular transporters. Confocal fluorescence microscopy revealed that Streptaphage-induced uptake of streptavidin functionally mimics the initial cellular penetration steps of Cholera toxin, which undergoes clathrin-mediated endocytosis upon binding

  大分子向活细胞的有效传递对开发有效的大分子疗法和细胞探针提出了巨大的挑战。我们在此描述了一种称为“链霉亲和素”的新型合成配体，它通过促进与胆固醇和细胞质膜的富含鞘脂的脂筏亚域的非共价相互作用，使细菌蛋白质链霉亲和素的有效细胞吸收成为可能。链球菌配体包含 3 β-胆固醇胺的 N-烷基衍生物，通过 11 个原子的系链与生物素的羧酸盐相连。链霉亲和素与这种膜结合配体之间的分子识别促进网格蛋白介导的内吞作用，这使得链霉亲和素在 10 分钟内部分进入细胞内，并在添加蛋白质后 4 小时内完全内化。通过落射荧光显微镜和流式细胞术对 Jurkat 淋巴细胞中的蛋白质摄取进行分析，发现细胞内荧光增强了 300 多倍（10 microM 配体），效率超过 99%，毒性低。其他哺乳动物细胞系包括 THP-1 巨噬细胞、MCF-7 乳腺癌细胞和 CHO 细胞也受到类似影响。带有较短接头或用等排酰胺取代质子化甾体胺
• [EN] CELLS LABELLED WITH LIPID CONJUGATES AND METHODS OF USE THEREOF<br/>[FR] CELLULES MARQUÉES PAR DES CONJUGUÉS LIPIDIQUES ET MÉTHODES D'UTILISATION DE CES DERNIÈRES
  申请人：UNIV CALIFORNIA

  公开号：WO2017079419A1

  公开（公告）日：2017-05-11

  A method of labelling a cell is provided. Aspects of the method include the contacting the cell with a cholesteryl-cargo conjugate having the formula: C-L-Z (I) wherein C is a cholesterylamine anchor group, L is an optional linker and Z is a linked cargo moiety to non-covalently bind the cholesterylamine anchoring group to the cell membrane thereby displaying Z at the cell surface for an extended period of time. Aspects of the method further include administering the labelled cell to a subject. Also provided is a method of modulating an immune response in a subject and a method of targeting a cell in a subject. Cholesterylamine conjugates, labelled cells and kits including the same that find use in the subject methods are also provided.

  提供了一种标记细胞的方法。该方法的方面包括使用具有以下公式的胆固醇-货物共轭物与细胞接触：C-L-Z（I），其中C是胆固醇胺锚定基，L是可选的连接物，Z是连接的货物基团，以非共价方式结合胆固醇胺锚定基到细胞膜上，从而在细胞表面显示Z，并延长其时间。该方法的方面还包括将标记的细胞给予受试者。还提供了一种调节受试者免疫反应的方法和一种在受试者中定位细胞的方法。还提供了胆固醇胺共轭物、标记的细胞和包括它们的试剂盒，这些试剂盒在上述方法中有用。
• A Synthetic Membrane-Anchored Antigen Efficiently Promotes Uptake of Antifluorescein Antibodies and Associated Protein A by Mammalian Cells
  作者：Stephen L. Hussey、Enfei He、Blake R. Peterson

  DOI：10.1021/ja017087o

  日期：2001.12.19

  The efficient delivery of small molecules, proteins, and DNA to living cells is critical for the effectiveness of therapeutics and molecular probes. Although most small-molecule drugs enter cells though passive diffusion across low-polarity cell membranes, macromolecules are typically not cell-permeable and require specific active transport mechanisms to gain access to intracellular receptors. 1 The

  小分子、蛋白质和 DNA 向活细胞的有效递送对于治疗和分子探针的有效性至关重要。尽管大多数小分子药物通过低极性细胞膜的被动扩散进入细胞，但大分子通常不具有细胞渗透性，需要特定的主动转运机制才能进入细胞内受体。1 天然和非天然分子的细胞摄取可以通过多种方法增强，包括用阳离子肽、2 种蛋白质、3 种拟肽、4 和脂质进行修饰、5 用脂质体、6 种树枝状聚合物、7 和铁载体、8 以及与阳离子聚合物复合. 9 然而，这些方法的效率差异很大，