tert-butyl N-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-N-[2-[(2-methylpropan-2-yl)oxycarbonyl-[2-[(2,2,2-trifluoroacetyl)amino]ethyl]amino]ethyl]carbamate | 1018998-67-8

• 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: tert-butyl N-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-N-[2-[(2-methylpropan-2-yl)oxycarbonyl-[2-[(2,2,2-trifluoroacetyl)amino]ethyl]amino]ethyl]carbamate
• CAS: 1018998-67-8
• 化学式: C₂₃H₄₁F₃N₄O₇
• 分子量: 542.596
• InChiKey: YARSWLKVWFUJAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  37
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-N-[2-[(2-methylpropan-2-yl)oxycarbonyl-[2-[(2,2,2-trifluoroacetyl)amino]ethyl]amino]ethyl]carbamate 在 水 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 以533.8 mg的产率得到N-aminoethyl-N,N'-bis(tert-butoxycarbonyl)-N-[(N-tert-butoxycarbonyl)aminoethyl]ethylenediamine
  参考文献：
  名称：

  Covalent functionalization of graphene sheets for plasmid DNA delivery: experimental and theoretical study

  摘要：

  石墨烯片与适当的连接体共价连接，成为向哺乳动物细胞传递 p-DNA 的新型载体。转染的癌细胞产生绿色荧光，表明基因传递成功。

  DOI：

  10.1039/d3ra00727h
• 作为产物：
  描述：

  三乙烯四胺 以 甲醇 为溶剂， 反应 25.75h， 生成 tert-butyl N-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-N-[2-[(2-methylpropan-2-yl)oxycarbonyl-[2-[(2,2,2-trifluoroacetyl)amino]ethyl]amino]ethyl]carbamate
  参考文献：
  名称：

  Covalent functionalization of graphene sheets for plasmid DNA delivery: experimental and theoretical study

  摘要：

  石墨烯片与适当的连接体共价连接，成为向哺乳动物细胞传递 p-DNA 的新型载体。转染的癌细胞产生绿色荧光，表明基因传递成功。

  DOI：

  10.1039/d3ra00727h

文献信息

• A Single Methylene Group in Oligoalkylamine-Based Cationic Polymers and Lipids Promotes Enhanced mRNA Delivery
  作者：Anita Jarzębińska、Tamara Pasewald、Jana Lambrecht、Olga Mykhaylyk、Linda Kümmerling、Philipp Beck、Günther Hasenpusch、Carsten Rudolph、Christian Plank、Christian Dohmen

  DOI：10.1002/anie.201603648

  日期：2016.8.8

  promise as a new class of biologic therapeutics. However, the intracellular delivery and endosomal escape of mRNA encapsulated in nanoparticles has not been systematically investigated. Here, we synthesized a diverse set of cationic polymers and lipids from a series of oligoalkylamines and subsequently characterized their mRNA delivery capability. Notably, a structure with an alternating alkyl chain length

  化学修饰的mRNA的发展作为一种新型的生物疗法具有广阔的前景。然而，尚未系统研究包裹在纳米颗粒中的mRNA的胞内递送和内体逃逸。在这里，我们从一系列的低聚烷基胺合成了各种阳离子聚合物和脂质，随后表征了它们的mRNA传递能力。值得注意的是，胺之间具有交替的烷基链长的结构显示出最高的转染效率，这与在pH 6.2至6.5的窄范围内的高缓冲能力有关。分别施用全身或气雾剂后，仅一个亚甲基的变化导致分别向鼠肝和猪肺的mRNA递送增强。
• LIPID CONTAINING FORMULATIONS
  申请人：Manoharan Muthiah

  公开号：US20090023673A1

  公开（公告）日：2009-01-22

  Compositions and methods useful in administering nucleic acid based therapies, for example association complexes such as liposomes and lipoplexes are described.

  本文介绍了用于管理基于核酸的治疗的组合物和方法，例如关联复合物，如脂质体和脂质复合物。
• WO2008/42973
  申请人：——

  公开号：——

  公开（公告）日：——
• Thiazole orange – Spermine conjugate: A potent human telomerase inhibitor comparable to BRACO-19
  作者：Siwen Wang、Dazhou Yang、Mandeep Singh、Hyun Joo、Vanessa M. Rangel、Aaron Tran、Erich Phan、Liang Xue

  DOI：10.1016/j.ejmech.2019.04.041

  日期：2019.8

  In this report, we synthesized a series of TO conjugates containing different amino side chains and investigated their binding to telomeric G-quadruplex DNA (G4) using several biophysical methods including fluorometric titration and thermal denaturation monitored by fluorescence and circular dichroism. The composition of side chains strongly affects the binding of these molecules to G-quadruplex DNA. Incorporation of amino side chains increases the binding affinity of TO toward G4 but has a minimal effect on its selectivity for G4 over duplex DNA. The plausible binding modes are a synergistic effect of end-stacking and groove interactions as indicated by docking studies. Inhibition of human telomerase activity by TO derivatives was determined in vitro by the TRAP assay. Several derivatives can selectively inhibit the activity of telomerase over DNA polymerase at low concentrations. More significantly, TO-spermine conjugate (16) exhibits a remarkable effect on telomerase inhibition in the submicromolar range, which is comparable to the inhibition effect of a well-known G4 ligand, BRACO-19. Our results here provide guidance of utilizing TO derivatives as a viable scaffold to design novel G4 ligands, G4 probes, and potent telomerase inhibitors. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Polycationic β-Cyclodextrin “Click Clusters”:  Monodisperse and Versatile Scaffolds for Nucleic Acid Delivery
  作者：Sathya Srinivasachari、Katye M. Fichter、Theresa M. Reineke

  DOI：10.1021/ja074597v

  日期：2008.4.1

  Herein, a novel series of multivalent polycationic beta-cycloclextrin "click clusters" with discrete molecular weight have been synthesized, characterized, and examined as therapeutic pDNA carriers. The materials were creatively designed based on a beta-cyclodextrin core to impart a biocompatible multivalent architecture and oligoethyleneamine arms to facilitate pDNA binding, encapsulation, and cellular uptake. An acetylated-per-azido-beta-cyclodextrin (4) was reacted with series of alkyne dendrons (7a-e) (containing one to five ethyleneamine units) using copper-catalyzed 1,3-dipolar cycloaddition, to form a series of click clusters (9a-e) bearing 1,2,3-triazole linkers. Gel electrophoresis experiments, dynamic light scattering, and transmission electron microscopy revealed that the macromolecules bind and compact pDNA into spherical nanoparticles in the size range of 80-130 nm. The polycations protect pDNA against nuclease degradation, where structures 9c, 9d, and 9e did not allow pDNA degradation in the presence of serum for up to 48 h. The cellular uptake profiles were evaluated in Opti-MEM and demonstrate that all the click clusters efficiently deliver Cy5-labeled pDNA into HeLa and H9c2 (2-1) cells, and compounds 9d and 9e yielded efficacy similar to that of the positive controls, Jet-PEI and Superfect. Furthermore, the luciferase gene delivery experiments revealed that the level of reporter gene expression increased with an increase in oligoethyleneamine number within the cluster arms. The cytotoxicity profiles of these materials were evaluated by protein, MTT, and LDH assays, which demonstrate that all the click clusters remain nontoxic within the expected dosage range while the positive controls, Jet PEI and Superfect, were highly cytotoxic. In particular, 9d and 9e were the most effective and promising polycationic vehicles to be further optimized for future systemic delivery experiments.