1-azido-4,9,13-tri(tert-butoxycarbonyl)-4,9,13-triazatridecane | 1190203-80-5

• 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: 1-azido-4,9,13-tri(tert-butoxycarbonyl)-4,9,13-triazatridecane
• 英文别名: Spermine(N3BBB)；tert-butyl N-(3-azidopropyl)-N-[4-[(2-methylpropan-2-yl)oxycarbonyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]butyl]carbamate
• CAS: 1190203-80-5
• 化学式: C₂₅H₄₈N₆O₆
• 分子量: 528.693
• InChiKey: OROLSMZGMDZZBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  37
• 可旋转键数：
  19
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  8

制备方法与用途

精胺（N3BBB）是一种含有叠氮基的点击化学试剂，可应用于多种生物化学研究。

反应信息

• 作为反应物：
  描述：

  1-azido-4,9,13-tri(tert-butoxycarbonyl)-4,9,13-triazatridecane 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 O₄S^(2-)*5H₂O*Cu⁽²⁺⁾*C₃₀H₃₀N₁₀ 、 sodium ascorbate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 71.0h， 生成 C₄₃H₇₄N₆O₃*3ClH
  参考文献：
  名称：

  两亲齐墩果酸-精胺结合物的快速自愈和触变有机胶凝

  摘要：

  天然和丰富的植物三萜是有吸引力的起始原料，用于合成功能性软材料的构象刚性和手性结构单元。在这里，我们报告了使用铜（I）催化的Huisgen 1,3-偶极环加成反应对目标分子中包含一个或两个精胺单元的三种齐墩果酸-三唑-精胺结合物的合理设计。生成的两亲性分子2和3，在各自的分子中仅带有一个精胺单元的分子，自组装成高度纠缠的纤维网络，导致在酒精溶剂中的凝胶化浓度低至0.5％。使用分步应变流变学测量，我们显示了快速自我恢复（高达初始储能模量的96％）和在几个循环中的sol凝胶转变。有趣的是，流变流动曲线揭示了凝胶的触变性。据我们所知，这种行为在三萜类化合物及其衍生物中都没有出现过。共轭4被发现具有类保兰两亲结构的非胶凝剂。我们的结果表明，精胺单元的位置和数量会改变胶凝特性，胶凝强度及其自组装行为。目标化合物的初步细胞毒性研究2 - 4在四种人类肿瘤细胞系表明的精胺单元的位置和数量影响生物活性。我

  DOI：

  10.1021/acs.langmuir.0c03335
• 作为产物：
  描述：

  精胺 在 copper(ll) sulfate pentahydrate 、 triflic azide 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 20.0h， 生成 1-azido-4,9,13-tri(tert-butoxycarbonyl)-4,9,13-triazatridecane
  参考文献：
  名称：

  Versatile Site-Specific Conjugation of Small Molecules to siRNA Using Click Chemistry

  摘要：

  We have previously demonstrated that conjugation of small molecule ligands to small interfering RNAs (siRNAs) and anti-microRNAs results in functional siRNAs and antagomirs in vivo. Here we report on the development of an efficient chemical strategy to make oligoribonucleotide-ligand conjugates using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) or click reaction. Three click reaction approaches were evaluated for their feasibility and suitability for high-throughput synthesis: the CuAAC reaction at the monomer level prior to oligonucleotide synthesis, the solution-phase postsynthetic "click conjugation", and the "click conjugation" on an immobilized and cornpletely protected alkyne-oligonucleotide scaffold. Nucleosides bearing 5'-alkyne moieties were used for conjugation to the 5'-end of the oligonucleotide. Previously described 2'- and 3'-O-propargylated nucleosides were prepared to introduce the alkyne moiety to the 3' and 5' termini and to the internal positions of the scaffold. Azido-functionalized ligands bearing lipophilic long chain alkyls, cholesterol, oligoamine, and carbohydrate were utilized to study the effect of physicochemical characteristics of the incoming azide on click conjugation to the alkyne-oligonucleotide scaffold in solution and on immobilized solid support. We found that microwave-assisted click conjugation of azido-functionalized ligands to a fully protected solid-support bound alkyne-oligonucleotide prior to deprotection was the most efficient "click conjugation" strategy for site-specific, high-throughput oligonucleotide conjugate synthesis tested. The siRNA conjugates synthesized using this approach effectively silenced expression of a luciferase gene in a stably transformed HeLa cell line.

  DOI：

  10.1021/jo101761g

文献信息

• Site specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
  申请人：Tekmira Pharmaceuticals Corporation

  公开号：US09345780B2

  公开（公告）日：2016-05-24

  The invention relates to compositions and methods for site-specific delivery of nucleic acids by combining them with targeting ligands and endosomolytic components.

  这项发明涉及将核酸与靶向配体和内体溶解组分结合，用于特定位点递送核酸的组合物和方法。
• CHEMICAL MODIFICATIONS OF MONOMERS AND OLIGONUCLEOTIDES WITH CYCLOADDITION
  申请人：Manoharan Muthiah

  公开号：US20120035115A1

  公开（公告）日：2012-02-09

  The invention features compounds of formula I or II: In one embodiment, the invention relates compounds and processes for conjugating ligand to oligonucleotide. The invention further relates to methods for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, cancers, allergies, autoimmune diseases, immunodeficiencies and immunosuppression.

  该发明涉及公式I或II的化合物：在一种实施方式中，该发明涉及化合物和用于将配体与寡核苷酸结合的过程。该发明进一步涉及治疗各种疾病和疾病的方法，例如病毒感染、细菌感染、寄生虫感染、癌症、过敏、自身免疫疾病、免疫缺陷和免疫抑制。
• Clickable Polyamine Derivatives as Chemical Probes for the Polyamine Transport System
  作者：Roeland Vanhoutte、Jan Pascal Kahler、Shaun Martin、Sarah van Veen、Steven H. L. Verhelst

  DOI：10.1002/cbic.201800043

  日期：2018.5.4

  Click to enter: Azide‐conjugated spermidine and spermine derivatives can easily be clicked onto alkyne‐containing cargo. Clicking a fluorophore yields spermidine and spermine probes that can be used to follow entry into the cell by the polyamine transport system.

  点击进入：叠氮化物共轭亚精胺和亚精胺衍生物可以轻松地点击到含炔的货物上。单击荧光团会产生亚精胺和精胺探针，可用于通过多胺转运系统进入细胞。
• Novel cytotoxic 1,10-phenanthroline–triterpenoid amphiphiles with supramolecular characteristics capable of coordinating ⁶⁴Cu(<scp>ii</scp>) labels
  作者：Uladzimir Bildziukevich、Zulal Özdemir、David Šaman、Martin Vlk、Miroslav Šlouf、Lucie Rárová、Zdeněk Wimmer

  DOI：10.1039/d2ob01172g

  日期：——

  Novel 1,10-phenanthroline–triterpenoid amphiphiles formed nano-assemblies in water, coordinated Cu(ii) and ⁶⁴Cu(ii) salts for potential cancer monitoring and therapy, and displayed cytotoxicity partly dependent on the formation of nano-assemblies.

  小说1,10-菲咯啉-三萜类两性分子在水中形成纳米组装体，与Cu(ii)和⁶⁴Cu(ii)盐协同作用，具有潜在的癌症监测和治疗作用，并且部分细胞毒性依赖于纳米组装体的形成。
• Novel Green Fluorescent Polyamines to Analyze ATP13A2 and ATP13A3 Activity in the Mammalian Polyamine Transport System
  作者：Marine Houdou、Nathalie Jacobs、Jonathan Coene、Mujahid Azfar、Roeland Vanhoutte、Chris Van den Haute、Jan Eggermont、Veronique Daniëls、Steven H. L. Verhelst、Peter Vangheluwe

  DOI：10.3390/biom13020337

  日期：——

  Cells acquire polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM) via the complementary actions of polyamine uptake and synthesis pathways. The endosomal P5B-type ATPases ATP13A2 and ATP13A3 emerge as major determinants of mammalian polyamine uptake. Our biochemical evidence shows that fluorescently labeled polyamines are genuine substrates of ATP13A2. They can be used to measure polyamine uptake in ATP13A2- and ATP13A3-dependent cell models resembling radiolabeled polyamine uptake. We further report that ATP13A3 enables faster and stronger cellular polyamine uptake than does ATP13A2. We also compared the uptake of new green fluorescent PUT, SPD and SPM analogs using different coupling strategies (amide, triazole or isothiocyanate) and fluorophores (symmetrical BODIPY, BODIPY-FL and FITC). ATP13A2 promotes the uptake of various SPD and SPM analogs, whereas ATP13A3 mainly stimulates the uptake of PUT and SPD conjugates. However, the polyamine linker and coupling position on the fluorophore impacts the transport capacity, whereas replacing the fluorophore affects polyamine selectivity. The highest uptake in ATP13A2 or ATP13A3 cells is observed with BODIPY-FL-amide conjugated to SPD, whereas BODIPY-PUT analogs are specifically taken up via ATP13A3. We found that P5B-type ATPase isoforms transport fluorescently labeled polyamine analogs with a distinct structure–activity relationship (SAR), suggesting that isoform-specific polyamine probes can be designed.

  细胞通过多胺摄取和合成途径的互补作用获得多胺--腐胺（PUT）、亚精胺（SPD）和精胺（SPM）。内体 P5B 型 ATP 酶 ATP13A2 和 ATP13A3 成为哺乳动物多胺摄取的主要决定因素。我们的生化证据表明，荧光标记的多胺是 ATP13A2 的真正底物。它们可用于测量 ATP13A2 和 ATP13A3 依赖性细胞模型中的多胺摄取，类似于放射性标记的多胺摄取。我们进一步报告说，与 ATP13A2 相比，ATP13A3 能使细胞更快、更强地吸收多胺。我们还比较了使用不同偶联策略（酰胺、三唑或异硫氰酸酯）和荧光团（对称 BODIPY、BODIPY-FL 和 FITC）的新型绿色荧光 PUT、SPD 和 SPM 类似物的摄取情况。ATP13A2 可促进各种 SPD 和 SPM 类似物的吸收，而 ATP13A3 则主要促进 PUT 和 SPD 共轭物的吸收。不过，多胺连接体和荧光团上的偶联位置会影响转运能力，而更换荧光团则会影响多胺的选择性。在 ATP13A2 或 ATP13A3 细胞中，与 SPD 共轭的 BODIPY-FL-amide 的吸收率最高，而 BODIPY-PUT 类似物则通过 ATP13A3 被特异性吸收。我们发现，P5B 型 ATP 酶同工酶转运荧光标记的多胺类似物具有不同的结构-活性关系（SAR），这表明可以设计同工酶特异性多胺探针。