(2S)-2-[[(2S)-4-carboxy-2-[[(2S)-3-carboxy-2-[[(2S)-2,6-diaminohexanoyl]amino]propanoyl]amino]butanoyl]amino]-4-methylpentanoic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-2-[[(2S)-4-carboxy-2-[[(2S)-3-carboxy-2-[[(2S)-2,6-diaminohexanoyl]amino]propanoyl]amino]butanoyl]amino]-4-methylpentanoic acid
• 化学式: C₂₁H₃₇N₅O₉
• 分子量: 503.5
• InChiKey: JBFQOLHAGBKPTP-AJNGGQMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.3
• 重原子数：
  35
• 可旋转键数：
  18
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  251
• 氢给体数：
  8
• 氢受体数：
  11

文献信息

• Methods Of Expressing And Detecting Activity of Expansin In Plant Cells
  申请人：Arkansas State University

  公开号：US20140325698A1

  公开（公告）日：2014-10-30

  A method of expressing heterologous expansin in a plant cell is provided where a nucleic acid molecule encoding expansin is introduced into the plant cell and in an embodiment is operably linked to a promoter preferentially expressing in the seed tissue of the plant, and in another embodiment is linked to a promoter preferentially expressing in the embryo tissue of the seed. An embodiment provides the nucleic acid molecule is operably linked to a second nucleic acid molecule that directs expression to the endoplasmic reticulum, vacuole or cell wall. Plants and plant parts expressing expansin are provided. An assay for detection of expansin activity is also provided.

  本发明提供了一种在植物细胞中表达异源扩张蛋白的方法，其中将编码扩张蛋白的核酸分子引入植物细胞，并在一种实施例中与优先表达植物种子组织的启动子操作链接，在另一种实施例中与优先表达种子胚芽组织的启动子链接。一种实施例提供将核酸分子与第二个核酸分子操作链接，以将表达定向到内质网、液泡或细胞壁。提供表达扩张蛋白的植物和植物部分。还提供了检测扩张蛋白活性的检测方法。
• Dual specific immunotoxin for brain tumor therapy
  申请人：Duke University

  公开号：US10072084B2

  公开（公告）日：2018-09-11

  We tested the in vitro and in vivo efficacy of a recombinant bispecific immunotoxin that recognizes both EGFRwt and tumor-specific EGFRvIII receptors. A single chain antibody was cloned from a hybridoma and fused to toxin, carrying a C-terminal peptide which increases retention within cells. The binding affinity and specificity of the recombinant bispecific immunotoxin for the EGFRwt and the EGFRvIII proteins was measured. In vitro cytotoxicity was measured. In vivo activity of the recombinant bispecific immunotoxin was evaluated in subcutaneous models and compared to that of an established monospecific immunotoxin. In our preclinical studies, the bispecific recombinant immunotoxin, exhibited significant potential for treating brain tumors.

  我们测试了一种重组双特异性免疫毒素的体外和体内疗效，这种毒素既能识别表皮生长因子受体（EGFRwt），也能识别肿瘤特异性表皮生长因子受体（EGFRvIII）。我们从杂交瘤中克隆了一种单链抗体，并将其与毒素融合，毒素的 C 端含有一种肽，可增加其在细胞内的保留率。测量了重组双特异性免疫毒素与表皮生长因子受体 wt 蛋白和表皮生长因子受体 vIII 蛋白的结合亲和力和特异性。测量了体外细胞毒性。在皮下模型中评估了重组双特异性免疫毒素的体内活性，并将其与已有的单特异性免疫毒素进行了比较。在我们的临床前研究中，双特异性重组免疫毒素在治疗脑肿瘤方面表现出了巨大的潜力。
• Combination therapy of immunotoxin and checkpoint inhibitor
  申请人：DUKE UNIVERSITY

  公开号：US11065332B2

  公开（公告）日：2021-07-20

  Regional, tumor-targeted, cytotoxic therapy, such as D2C7-immunotoxin (D2C7-IT), not only specifically target and destroy tumor cells, but in the process initiate immune events that promote an in situ vaccine effect. The antitumor effects are amplified by immune checkpoint blockade which engenders a long-term systemic immune response that effectively eliminates all tumor cells.

  区域性肿瘤靶向细胞毒性疗法，如 D2C7-免疫毒素（D2C7-IT），不仅能特异性地靶向破坏肿瘤细胞，还能在此过程中启动免疫事件，促进原位疫苗效应。免疫检查点阻断可增强抗肿瘤效果，从而产生长期的全身免疫反应，有效清除所有肿瘤细胞。
• Selective destruction of cells infected with human immunodeficiency virus
  申请人：——

  公开号：US20020094334A1

  公开（公告）日：2002-07-18

  Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  本研究公开了选择性杀死含有病毒蛋白酶的细胞的组合物和方法。该组合物是一种蛋白质合成失活毒素的变体，其中病毒蛋白酶裂解位点位于 A 链和 B 链之间。通过特异性病毒蛋白酶消化病毒蛋白酶裂解位点，激活 II 型核糖体失活蛋白变体。活化后的核糖体灭活蛋白通过使细胞核糖体失活而杀死细胞。本发明的一个优选实施方案对人类免疫缺陷病毒（HIV）具有特异性，并使用蓖麻毒素作为核糖体失活蛋白。在本发明的另一个优选实施方案中，核糖体失活蛋白的变体通过附着一种或多种疏水剂进行修饰。疏水剂有利于核糖体灭活蛋白变体进入细胞，并可将核糖体灭活蛋白纳入病毒颗粒。本发明的另一个优选实施方案包括与核糖体灭活蛋白变体相连的靶向分子，以便将制剂靶向于可感染艾滋病毒的细胞。
• Compositions and methods for the transport of biologically active agents across cellular barriers
  申请人：——

  公开号：US20030161809A1

  公开（公告）日：2003-08-28

  Disclosed herein are complexes and compounds that pass through cellular barriers to deliver compounds into, through and out of cells, and methods of producing and using such complexes and compounds. The complexes and compounds of the invention comprise a biologically active portion and a targeting element directed to a ligand that confers transcellular, transcytotic or paracellular transporting properties to an agent specifically bound to the ligand, with the proviso that the targeting element is not an antibody. Also disclosed are complexes and compounds that comprise two or more targeting elements directed to a ligand that confers transcellular, transcytotic or paracellular transporting properties to an agent specifically bound to the ligand. Preferred ligands include but are not limited to the stalk of pIgR, a pIgR domain, an amino acid sequence that is conserved among pIgR's from different animals, and one of several regions of pIgR defined herein.

  本发明公开了可穿过细胞屏障将化合物送入、穿过和排出细胞的复合物，以及生产和使用此类复合物的方法。本发明的复合物和化合物包括生物活性部分和靶向配体的靶向元件，该配体可使与配体特异性结合的药剂具有跨细胞、跨细胞或细胞旁转运特性，但靶向元件不是抗体。此外，还公开了由两个或多个靶向元件组成的配合物和化合物，这些靶向元件指向一种配体，该配体可使与配体特异性结合的药剂具有跨细胞、跨细胞或细胞旁转运特性。优选的配体包括但不限于 pIgR 的柄、pIgR 结构域、不同动物的 pIgR 之间保守的氨基酸序列以及本文定义的 pIgR 的几个区域之一。