(10S)-2,2,21,21-四甲基-4,19-二氧代-3,20-二氧杂-5,9,14,18-四氮杂二十二烷-9,10,14-三羧酸 9,14-二叔丁酯 | 119798-08-2

• 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
• 中文名称: (10S)-2,2,21,21-四甲基-4,19-二氧代-3,20-二氧杂-5,9,14,18-四氮杂二十二烷-9,10,14-三羧酸 9,14-二叔丁酯
• 中文别名: (10S)-2,2,21,21-四甲基-4,19-二氧代-3,20-二氧杂-5,9,14,18-四氮杂二十二烷-9,10,14-三羧酸9,14-二叔丁酯
• 英文名称: N²,N⁵-Bis[(1,1-dimethylethoxy)carbonyl]-N²,N⁵-bis[3-[(1,1-dimethylethoxy)-carbonyl]aminopropyl]-L-ornithine
• 英文别名: N2,N5-bis[(1,1-dimethylethoxy)carbonyl]-N2,N5-bis[3-[(1,1-dimethylethoxy)carbonyl]amino-propyl]-L-ornithine；Nα,Nδ-bis(Boc)-Nα,Nδ-bis(3-[Boc-amino]propyl)ornithine；N2,N5-Bis[(1,1-dimethylethoxy)carbonyl]-N2,N5-bis[3-[(1,1-dimethylethoxy)carbonyl]aminopropyl]-L-ornithine；tetra-Boc-spermine-5-carboxylic acid；(2S)-2,5-bis[(2-methylpropan-2-yl)oxycarbonyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]pentanoic acid
• CAS: 119798-08-2
• 化学式: C₃₁H₅₈N₄O₁₀
• 分子量: 646.822
• InChiKey: HSPKBBVFWXCYJN-QFIPXVFZSA-N

物化性质

• 熔点：
  67 - 70°C
• 沸点：
  737.1±60.0 °C(Predicted)
• 密度：
  1.112±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  45
• 可旋转键数：
  22
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  173
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (10S)-2,2,21,21-四甲基-4,19-二氧代-3,20-二氧杂-5,9,14,18-四氮杂二十二烷-9,10,14-三羧酸 9,14-二叔丁酯 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 2,3-dioleoyloxy-N-[2-(spermine-carboxamido)ethyl]-N,N-dimethyl-1-propanaminum chloride
  参考文献：
  名称：

  一种高效合成阳离子脂质 DOSPA 的方法

  摘要：

  已经开发了一种高效的合成阳离子脂质的策略，N-[2-({2,5-双[(3-氨基丙基)氨基]-1-氧代戊基}氨基)乙基]-N,N-二甲基-2,3-双[(1-oxo-9-octadecenyl)oxy] 与氯化氢的盐 (DOSPA)。它涉及在标准偶联剂存在下连接阳离子头基和疏水部分。

  DOI：

  10.1055/s-2006-949636
• 作为产物：
  描述：

  L-鸟氨酸盐酸盐 在 镍 sodium hydroxide 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 20.0 ℃ 、413.68 kPa 条件下， 反应 32.0h， 生成 (10S)-2,2,21,21-四甲基-4,19-二氧代-3,20-二氧杂-5,9,14,18-四氮杂二十二烷-9,10,14-三羧酸 9,14-二叔丁酯
  参考文献：
  名称：

  A Columnar Phase of Dendritic Lipid−Based Cationic Liposome−DNA Complexes for Gene Delivery:  Hexagonally Ordered Cylindrical Micelles Embedded in a DNA Honeycomb Lattice

  摘要：

  Gene therapy holds great promise as a future approach to fighting disease and is explored in worldwide clinical trials. Cationic liposome (CL)-DNA complexes are a prevalent nonviral delivery vector, but their efficiency requires improvement and the understanding of their mechanism of action is incomplete. As part of our effort to investigate the structure-transfection efficiency relationships of self-assembled CL-DNA vectors, we have synthesized a new, highly charged (16+) multivalent cationic lipid, MVLBG2, with a dendritic headgroup. Our synthetic scheme allows facile variation of the headgroup charge and the spacer connecting hydrophobic and headgroup moieties as well as gram-scale synthesis. Complexes of DNA with mixtures of MVLBG2 and neutral 1,2-dioleoyl-sn-glycerophosphatidylcholine (DOPC) exhibit the well-known lamellar phase at 90 mol % DOPC. Starting at 20 mol % dendritic lipid, however, two novel nonlamellar phases are observed by synchrotron X-ray diffraction. The structure of one of these phases, present in a narrow range of composition around 25 mol % MVLBG2, has been solved. In this novel dual lattice structure, termed H-l(C), hexagonally arranged tubular lipid micelles are surrounded by DNA rods forming a three-dimensionally continuous substructure with honeycomb symmetry. Complexes in the H-l(C) phase efficiently transfect mouse and human cells in culture. Their transfection efficiency, as well as that of the lamellar complexes containing only 10 mol % dendritic lipid, reaches and surpasses that of commercially available, optimized DOTAP-based complexes. In particular, complexes containing MVLBG2 are significantly more transfectant over the entire composition range in mouse embryonic fibroblasts, a cell line empirically known to be hard to transfect.

  DOI：

  10.1021/ja055907h

文献信息

• Amide-based cationic lipids
  申请人：Promega Biosciences, Inc.

  公开号：US06339173B1

  公开（公告）日：2002-01-15

  The present invention provides novel amide-based cationic lipids of the general structure: or a salt, or solvate, or enantiomers thereof wherein; (a) Y is a direct link or an alkylene of 1 to about 20 carbon atoms; (b) R1 is H or a lipophilic moiety; (c) R2, R3, and R4 are positively charged moieties, or at least one but not all of R2,R3, or R4 is a positive moiety and the remaining are independently selected from H, an alkyl moiety of 1 to about 6 carbon atoms, or a heterocyclic moiety of about 5 to about 10 carbon atoms; (d) n and p are independently selected integers from 0 to 8, such that the sum of n and o is from 1 to 16; (e) X− is an anion or polyanion and (f) m is an integer from 0 to a number equivalent to the positive charge(s) present on the lipid; provided that if Y is a direct link and the sum of n and p is 1 then one of either R3 or R4 must have an alkyl moiety of at least 10 carbon atoms. The present invention further provides compositions of these lipids with polyanionic macromolecules, methods for interfering with protein expression in a cell utilizing these compositions and a kit for preparing the same.

  本发明提供了一种新型的基于酰胺的阳离子脂质，其一般结构如下： 或其盐、溶剂合物、对映体，其中；(a) Y是直链或1至约20个碳原子的烷基；(b) R1是H或亲脂性基团；(c) R2、R3和R4是带正电荷的基团，或者R2、R3或R4中至少一个而不是全部是正电荷基团，其余的可独立选择自H、1至约6个碳原子的烷基或约5至约10个碳原子的杂环基团；(d) n和p是独立选择的0至8的整数，使得n和o的总和为1至16；(e) X-是阴离子或多阴离子，(f) m是0到与脂质上存在的正电荷数等效的数字；但如果Y是直链且n和p的总和为1，则R3或R4中的一个必须具有至少10个碳原子的烷基。本发明还提供了这些脂质与多阴离子大分子的组合物，利用这些组合物干扰细胞中蛋白质表达的方法以及用于制备相同的试剂盒。
• Precision Templating with DNA of a Virus-like Particle with Peptide Nanostructures
  作者：Yves Ruff、Tyson Moyer、Christina J. Newcomb、Borries Demeler、Samuel I. Stupp

  DOI：10.1021/ja4008003

  日期：2013.4.24

  formed by self-assembly of coiled-coil peptides conjugated at opposite termini with cationic segments and poly(ethylene glycol) (PEG) chains. We found that a high molecular weight of PEG segments was critical for the formation of monodisperse and uniformly shaped filamentous complexes. It is proposed that electrostatic attachment of the nanostructures with sufficiently long PEG segments generates steric

  我们在这里报告了通过封装线性或圆形双链 DNA 模板来制备丝状病毒样颗粒，该模板具有带正电荷的域的预组装蘑菇形纳米结构。这些纳米结构模拟天然丝状病毒的衣壳蛋白，由卷曲螺旋肽在相对末端与阳离子片段和聚（乙二醇）（PEG）链共轭的自组装形成。我们发现高分子量的 PEG 片段对于形成单分散且形状均匀的丝状复合物至关重要。有人提出，具有足够长 PEG 片段的纳米结构的静电附着会产生空间力，从而增加中和的 DNA 模板的刚度。这种硬化抵消了 DNA 模板凝结成环形或多次弯曲的自然趋势。对颗粒的形状和尺寸实现的控制提供了一种策略来创建包含核酸的定义长度的一维超分子纳米结构。
• Novel amide-based cationic lipids
  申请人：Promega Biosciences, Inc.

  公开号：US20020156237A1

  公开（公告）日：2002-10-24

  The present invention provides novel amide-based cationic lipids of the general structure: 1 or a salt, or solvate, or enantiomers thereof wherein; (a) Y is a direct link or an alkylene of 1 to about 20 carbon atoms; (b) R 1 is H or a lipophilic moiety; (c) R 2 , R 3 , and R 4 are positively charged moieties, or at least one but not all of R 2 , R 3 , or R 4 , is a positive moiety and the remaining are independently selected from H, an alkyl moiety of 1 to about 6 carbon atoms, or a heterocyclic moiety of about 5 to about 10 carbon atoms; (d) n and p are independently selected integers from 0 to 8, such that the sum of n and o is from 1 to 16; (e) X − is an anion or polyanion and (f) m is an integer from 0 to a number equivalent to the positive charge(s) present on the lipid; provided that if Y is a direct link and the sum of n and p is 1 then one of either R 3 or R 4 must have an alkyl moiety of at least 10 carbon atoms. The present invention further provides compositions of these lipids with polyanionic macromolecules, methods for interfering with protein expression in a cell utilizing these compositions and a kit for preparing the same.

  本发明提供了一般结构的新型酰胺基阳离子脂： 1 或其盐，或其溶解物，或其对映体 其中；(a) Y 是直链或 1 至约 20 个碳原子的亚烷基；(b) R 1 是 H 或亲脂分子； (c) R 2 , R 3 和 R 4 是带正电荷的分子，或 R 2 , R 3 或 R 4 (d) n 和 p 是独立选取的 0 至 8 的整数，使得 n 和 o 之和为 1 至 16； (e) X - 是阴离子或多阴离子；(f) m 是 0 至相当于脂质上存在的正电荷的整数；但如果 Y 是直接连接，且 n 和 p 之和为 1，则 R 3 或 R 4 必须具有至少 10 个碳原子的烷基。 本发明进一步提供了这些脂质与多阴离子大分子的组合物、利用这些组合物干扰细胞中蛋白质表达的方法以及制备这些组合物的试剂盒。
• Synthesis and characterization of degradable multivalent cationic lipids with disulfide-bond spacers for gene delivery
  作者：Rahau S. Shirazi、Kai K. Ewert、Cecilia Leal、Ramsey N. Majzoub、Nathan F. Bouxsein、Cyrus R. Safinya

  DOI：10.1016/j.bbamem.2011.04.020

  日期：2011.9

  Gene therapy provides powerful new approaches to curing a large variety of diseases, which are being explored in ongoing worldwide clinical trials. To overcome the limitations of viral gene delivery systems, synthetic nonviral vectors such as cationic liposomes (CLs) are desirable. However, improvements of their efficiency at reduced toxicity and a better understanding of their mechanism of action are required. We present the efficient synthesis of a series of degradable multivalent cationic lipids (CMVLn, n=2 to 5) containing a disulfide bond spacer between headgroup and lipophilic tails. This spacer is designed to be cleaved in the reducing milieu of the cytoplasm and thus decrease lipid toxicity. Small angle X-ray scattering demonstrates that the initially formed lamellar phase of CMVLn-DNA complexes completely disappears when reducing agents such as DTT or the biologically relevant reducing peptide glutathione are added to mimic the intracellular milieu. The CMVLs (n=3 to 5) exhibit reduced cytotoxicity and transfect mammalian cells with efficiencies comparable to those of highly efficient non-degradable analogs and benchmark commercial reagents such as Lipofectamine 2000. Thus, our results demonstrate that degradable disulfide spacers may be used to reduce the cytotoxicity of synthetic nonviral gene delivery carriers without compromising their transfection efficiency. (C) 2011 Elsevier B.V. All rights reserved.
• Facile Quantification of Lesions Derived from 2‘-Deoxyguanosine in DNA
  作者：Liang Xue、Marc M. Greenberg

  DOI：10.1021/ja072174n

  日期：2007.6.6

  OxodG and Fapy center dot dG are two frequently formed DNA lesions that affect replication in vitro and in cells. They are also potentially important biomarkers for determining the effects of oxidative stress and aging in cells. We report the first method that enables one to selectively detect and individually quantify Fapy center dot dG and OxodG in DNA. The method relies upon selective chemical trapping of oxidized forms of the lesions with a biotinylated derivative of spermine. Selectivity for OxodG over Fapy center dot dG is achieved by varying the oxidant. The covalently tagged lesions are quantified using a fluorescence assay that is carried out in microtiter plates. The fluorescence assay is generally applicable to quantifying DNA lesions that can be tagged with biotin.