bis(2-propynoylaminoethyl)carbamic acid tert-butyl ester | 888327-59-1

• 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: bis(2-propynoylaminoethyl)carbamic acid tert-butyl ester
• 英文别名: tert-butyl N,N'-bis[ethylene(2-propynamide)]carbamate；tert-butyl N,N-bis[2-(prop-2-ynoylamino)ethyl]carbamate
• CAS: 888327-59-1
• 化学式: C₁₅H₂₁N₃O₄
• 分子量: 307.349
• InChiKey: WJBFAETZJIYJGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  bis{2-[(2,2,2-trifluoroacetyl)amino]ethyl}carbamic acid tert-butyl ester 在 potassium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 bis(2-propynoylaminoethyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  Trehalose Click Polymers Inhibit Nanoparticle Aggregation and Promote pDNA Delivery in Serum

  摘要：

  Herein, three new glycopolymers have been synthesized via "click polymerization" to promote nucleic acid delivery in the presence of biological media containing serum. These structures were designed to contain a trehalose moiety to promote biocompatibility, water solubility, and stability against aggregation, amide-triazole groups to enhance DNA binding affinity, and an oligoamine unit to facilitate DNA encapsulation, phosphate neutralization, and interactions with cell surfaces. A 2,3,4,2', 3', 4'-hexa-O-acetyl-6,6'-diazido-6,6'-dideoxy-(D)-trehalose (4) monomer was polymerized via copper(I)-catalyzed azide-alkyne cycloaddition with a series of dialkyne-amide comonomers that contain either one, two, or three Boc-protected secondary amines (7a, 7b, or 7c, respectively). After deprotection, three water-soluble polycations (9a, 9b, or 9c) were obtained with similar degrees of polymerization (n = 56-61) to elucidate the role of amine number on nucleic acid binding, complex formation, stability, and cellular delivery. Gel electrophoresis and ethidium bromide experiments showed that 9a-9c associated with plasmid DNA (pDNA) and formed complexes (polyplexes) at N/P ratios dependent on the amine number. TEM experiments revealed that 9a-9c polyplexes were small (50-120 nm) and had morphologies (spherical and rodlike) associated with the polymer chain stiffness. Dynamic light scattering studies in the presence of media containing serum demonstrated that 9c polyplexes had a low degree of flocculation, whereas 9a and 9b polyplexesd aggregate rapidly. Further biological studies revealed that these structures were biocompatible and deliver pDNA into HeLa cells. Particularly, 9c polyplexes promoted high delivery efficacy and gene expression profiles in the presence of serum.

  DOI：

  10.1021/ja0585580

文献信息

• OLIGONUCLEOTIDE DECOYS AND METHODS OF USE
  申请人：Jones Walter Keith

  公开号：US20090099108A1

  公开（公告）日：2009-04-16

  The present invention describes reagents and methods for using a concatemerized double-stranded oligonucleotide molecules (CODN) for transcription factor decoys. In one embodiment, the concatemers consist of a variable number of end-to-end repeated copies of a short (more than 5, 10, 15, 20, 2, 3035, 40, 45, 50, 75, 100, or more by but generally less than about 3 kb) dsDNA containing a sequence or sequences that act as transcription factor decoys. The present invention also provides for the use of the polymers for CODN/polymer complexes to a specific cell type; thus the agent can be made organ, tissue and/or cell-type specific. In another embodiment, the present invention provides for use of the CODN's in vitro or in vivo, in isolated cells or intact animals in which specific blockade of transcription factors or delivery of DNA or other biological effector is desirable. In one embodiment, this includes use as a research tool, including studies of specific genes and studies to identify specific genes regulated by the transcription factors targeted. In another embodiment, the present invention provides for using polyamides for NF-kB-specific CODN delivery in the treatment of myocardial ischemia/reperfusion and myocardial infarction, heart failure and hypertrophy, cardioprotection, stroke, neuroprotection, sepsis, arthritis, asthma, heritable inflammatory disorders, cancer, heritable immune dysfunctions, inflammatory processes, whether caused by disease or injury or infection, oxidative stress to any organ whether caused by disease, surgery or injury. The decoys may be any transcription factors, including, but not limited to, NF-kB, AP-I, ATF2, ATF3, SP 1 and others.

  本发明描述了一种使用串联双链寡核苷酸分子（CODN）作为转录因子诱饵的试剂和方法。在一种实施例中，串联体由一种短的（大于5、10、15、20、25、30、35、40、45、50、75、100或更多，但通常小于约3 kb）双链DNA的端对端重复拷贝构成，其中包含作为转录因子诱饵的一个或多个序列。本发明还提供了将聚合物用于CODN/聚合物复合物对特定细胞类型的使用；因此，该试剂可以被制成特定的器官、组织和/或细胞类型。在另一种实施例中，本发明提供了在离体或体内、在孤立的细胞或完整的动物中使用CODN的方法，其中需要特定的转录因子阻断或DNA或其他生物效应物的递送。在一种实施例中，这包括用作研究工具，包括研究特定基因和研究识别被靶向的转录因子调控的特定基因。在另一种实施例中，本发明提供了使用聚酰胺进行NF-kB特异性CODN递送，用于治疗心肌缺血/再灌注和心肌梗死、心力衰竭和肥厚、心脏保护、中风、神经保护、败血症、关节炎、哮喘、遗传性炎症性疾病、癌症、遗传性免疫功能障碍、炎症过程，无论是由疾病、手术还是损伤或感染引起的，以及对任何器官的氧化应激。诱饵可以是任何转录因子，包括但不限于NF-kB、AP-I、ATF2、ATF3、SP1等。
• Linear Cationic Click Polymer for Gene Delivery: Synthesis, Biocompatibility, and In Vitro Transfection
  作者：Yu Gao、Lingli Chen、Zhiwen Zhang、Wangwen Gu、Yaping Li

  DOI：10.1021/bm100906m

  日期：2010.11.8

  Sixteen novel cationic click polymers (CPs) were parallelly synthesized via the conjugation of our alkyne-functionalized monomers to four azide-functionalized monomers by "click chemistry". The biocompatibility of CPs was evaluated by in vitro cytotoxicity (MTT assay, Hoechst/PI apoptosis/necrosis assay, and cell cycle analysis) and blood compatibility tests (hemolysis and erythrocyte aggregation). The experimental results showed that the kind of amine groups, charge density, and number of methylene or ethylene glycol groups brought about the effect on toxicity of CPs. Among all polymers, two polymers (B-1 and B-2) showed good biocompatibility. inducing neither apoptosis nor necrosis at the test concentration and low hemolysis ratio and erythrocyte aggregation. In particular, B-1 and B-2 exhibited the comparable transfection efficiency compared with PEI (25 kDa) but much lower cytotoxicity. These results suggested that the novel cationic CPs could be promising carriers for gene delivery.
• POLYAMIDES FOR NUCLEIC ACID DELIVERY
  申请人：Reineke Theresa M.

  公开号：US20090105115A1

  公开（公告）日：2009-04-23

  The present invention provides a new class of non-viral transduction vectors that can be used for both in vivo and in vitro applications. The present invention also provides a gene transfer vector that has comparable efficiency to a viral vector without the potential for a life-threatening immune response. Complexes according to the invention or portions thereof, can comprise a cellular delivery molecule or agent that can facilitate the translocation of the complex or portion thereof into cells. In some embodiments, cellular delivery molecules for use in the present invention may comprise one or more polymers of the present invention, e.g., polyamides, dendritic macromolecules and carbohydrate-containing degradable polyesters.
• Trehalose Click Polymers for Delivery of Biologically Active Molecules
  申请人：Reineke Theresa Marie

  公开号：US20090124534A1

  公开（公告）日：2009-05-14

  Novel trehalose click polymers have in vitro and in vivo application in the cellular delivery of biologically active molecules, including nucleic acids and polypeptides. The trehalose click polymers of the present invention provide increased stability in serum as compared with other non-viral vectors, and are particularly useful in protecting nucleic acids against degradation.
• Polyamides For Nucleic Acid Delivery
  申请人：Reineke Theresa M.

  公开号：US20120270927A1

  公开（公告）日：2012-10-25

  A new class of non-viral transduction vectors that can be used for both in vivo and in vitro applications, including, a gene transfer vector that has comparable efficiency to a viral vector without the potential for a life-threatening immune response is provided. Complexes including a cellular delivery molecule or agent that can facilitate the translocation of the complex or portion thereof into cells is also provided. The cellular delivery molecules may include one or more polymers, e.g., polyamides, dendritic macromolecules and carbohydrate-containing degradable polyesters.