1-azido-11-phthalimido-3,6,9-trioxaundecane | 134179-44-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 1-azido-11-phthalimido-3,6,9-trioxaundecane
• 英文别名: Phthalamide-PEG3-azide；2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethyl]isoindole-1,3-dione
• CAS: 134179-44-5
• 化学式: C₁₆H₂₀N₄O₅
• 分子量: 348.359
• InChiKey: BEELPXILEIOFRO-UHFFFAOYSA-N

物化性质

• 熔点：
  >200 °C (decomp)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  79.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-azido-11-phthalimido-3,6,9-trioxaundecane 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以92%的产率得到1-氨基-11-叠氮-3,6,9-三氧杂十一烷
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Original Carriers for Targeting Vascular Endothelial Growth Factor Receptor Interactions

  摘要：

  血管生成是肿瘤生长和转移、慢性炎症疾病以及心血管疾病中的关键事件。它受到正负调节因子的控制，其中血管内皮生长因子（VEGF）是最为活跃的分子之一。VEGF/VEGF受体不仅是治疗的重要靶点，也是成像的关键目标。基于对VEGF结构的深入研究，我们开发出一种新型的环状肽（cyclo-VEGI），展现出强大的抗癌性能。本文报道了从cyclo-VEGI衍生的新型分子设计，旨在作为癌症和其他与血管生成相关疾病中的潜在靶向试剂。我们对源自VEGF的最活跃的环肽（cyclo-VEGI）进行了选择性的化学修饰。合成了原有的亲水性连接体并结合到cyclo-VEGI上，这些反应为递送提供了纳米载体。通过与125I-VEGF的竞争性试验，评估了不同化合物对VEGF结合的抑制效果。制作了荧光标记的cyclo-VEGI肽，以评估其直接结合及内化情况。化学修饰后的cyclo-VEGI并未降低其生物活性，在竞争性试验中甚至有所增强。此外，荧光标记的cyclo-VEGI在细胞内积累显著。本研究所合成的缀合物有望成为设计癌症和其他血管生成相关疾病靶向递送系统的有用先导。改良的cyclo-VEGI具有广泛的潜在应用，并可能成为开发治疗靶向或成像递送/载体系统的有效工具。

  DOI：

  10.1007/s11095-005-5265-9
• 作为产物：
  描述：

  13,13,14,14-四甲基-3,6,9,12-四氧杂-13-硅-1-十五醇 在 sodium azide 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 1-azido-11-phthalimido-3,6,9-trioxaundecane
  参考文献：
  名称：

  The synthesis of heterobifunctional linkers for the conjugation of ligands to molecular probes

  摘要：

  DOI：

  10.1021/jo00013a053

文献信息

• Design, Synthesis, and Evaluation of Original Carriers for Targeting Vascular Endothelial Growth Factor Receptor Interactions
  作者：Mario Gonçalves、Karine Estieu-Gionnet、Thomas Berthelot、Georges Laïn、Mireille Bayle、Xavier Canron、Natacha Betz、Andreas Bikfalvi、Gérard Déléris

  DOI：10.1007/s11095-005-5265-9

  日期：2005.8

  Angiogenesis is a key event in tumor growth and metastasis, chronic inflammatory disease, and cardiovascular disease. It is controlled by positive and negative regulators, which include vascular endothelial growth factor (VEGF) as the most active of these. VEGF/VEGF receptors are important targets not only for therapy but also for imaging. Based on the structural study of VEGF, we developed a novel cyclopeptide (cyclo-VEGI) that exhibits powerful antitumor properties. We herein report the design of novel molecules derived from cyclo-VEGI as potential targeting agents in cancer and other angiogenesis-related diseases. We performed selective chemical modification of the most active VEGF-derived cyclopeptide (cyclo-VEGI). Original hydrophilic linkers were synthesized and coupled to cyclo-VEGI. These reactions provide nanocarriers for delivery. The inhibitory effect of the different compounds on VEGF binding was evaluated in competition assays with 125I-VEGF. A fluorescent cyclo-VEGI peptide was synthezised to assess direct binding and internalization of cyclo-VEGI. Chemical modifications of cyclo-VEGI do not diminish the biological activity of cyclo-VEGI as measured in competition assays; in fact, it is even increased. Moreover there is a strong cellular accumulation of the fluorescent-labeled cyclo-VEGI. Conjugates synthesized in this study may be useful leads to design delivery systems for targeting approaches in cancer and other angiogenesis-related diseases. The modified cyclo-VEGIs may have a wide range of applications and represent a useful tool to develop delivery/carrier systems for therapeutic targeting or imaging.

  血管生成是肿瘤生长和转移、慢性炎症疾病以及心血管疾病中的关键事件。它受到正负调节因子的控制，其中血管内皮生长因子（VEGF）是最为活跃的分子之一。VEGF/VEGF受体不仅是治疗的重要靶点，也是成像的关键目标。基于对VEGF结构的深入研究，我们开发出一种新型的环状肽（cyclo-VEGI），展现出强大的抗癌性能。本文报道了从cyclo-VEGI衍生的新型分子设计，旨在作为癌症和其他与血管生成相关疾病中的潜在靶向试剂。我们对源自VEGF的最活跃的环肽（cyclo-VEGI）进行了选择性的化学修饰。合成了原有的亲水性连接体并结合到cyclo-VEGI上，这些反应为递送提供了纳米载体。通过与125I-VEGF的竞争性试验，评估了不同化合物对VEGF结合的抑制效果。制作了荧光标记的cyclo-VEGI肽，以评估其直接结合及内化情况。化学修饰后的cyclo-VEGI并未降低其生物活性，在竞争性试验中甚至有所增强。此外，荧光标记的cyclo-VEGI在细胞内积累显著。本研究所合成的缀合物有望成为设计癌症和其他血管生成相关疾病靶向递送系统的有用先导。改良的cyclo-VEGI具有广泛的潜在应用，并可能成为开发治疗靶向或成像递送/载体系统的有效工具。
• Design and synthesis of protoporphyrin IX/vitamin<font>B₁₂</font>molecular hybrids<i>via</i><font>CuAAC</font>reaction
  作者：Rafał Loska、Anita Janiga、Dorota Gryko

  DOI：10.1142/s1088424612501350

  日期：2013.1

  The design and synthesis of new molecular hybrids composed of protoporphyrin IX (PPIX) and vitamin B₁₂via copper catalyzed alkyne azide cycloaddition reaction is described. New, clickable aminoazide and aminoalkyne linkers were prepared and subsequently attached to PPIX (via vinyl group) and to vitamin B₁₂giving desired building blocks. Preliminary results showed that respective water soluble hybrids were formed under CuAAC reaction. Gratifyingly, Cu incorporation into the PPIX core was avoided, which was important for further biological studies.

  本文介绍了通过铜催化炔吖啶环加成反应设计和合成由原卟啉 IX（PPIX）和维生素 B12 组成的新分子杂化物。研究人员制备了新的、可点击的氨基吖啶和氨基炔连接体，随后将其连接到 PPIX（通过乙烯基）和维生素 B12 上，得到了所需的构建模块。初步结果表明，在 CuAAC 反应中形成了各自的水溶性混合物。令人欣慰的是，Cu 并入 PPIX 核心的情况得以避免，这对进一步的生物研究非常重要。
• Efficient synthesis of diverse heterobifunctionalized clickable oligo(ethylene glycol) linkers: potential applications in bioconjugation and targeted drug delivery
  作者：Lalit N. Goswami、Zachary H. Houston、Saurav J. Sarma、Satish S. Jalisatgi、M. Frederick Hawthorne

  DOI：10.1039/c2ob26968f

  日期：——

  Herein we describe the sequential synthesis of a variety of azide-alkyne click chemistry-compatible heterobifunctional oligo(ethylene glycol) (OEG) linkers for bioconjugation chemistry applications. Synthesis of these bioorthogonal linkers was accomplished through desymmetrization of OEGs by conversion of one of the hydroxyl groups to either an alkyne or azido functionality. The remaining distal hydroxyl group on the OEGs was activated by either a 4-nitrophenyl carbonate or a mesylate (–OMs) group. The –OMs functional group served as a useful precursor to form a variety of heterobifunctionalized OEG linkers containing different highly reactive end groups, e.g., iodo, –NH2, –SH and maleimido, that were orthogonal to the alkyne or azido functional group. Also, the alkyne- and azide-terminated OEGs are useful for generating larger discrete poly(ethylene glycol) (PEG) linkers (e.g., PEG16 and PEG24) by employing a Cu(I)-catalyzed 1,3-dipolar cycloaddition click reaction. The utility of these clickable heterobifunctional OEGs in bioconjugation chemistry was demonstrated by attachment of the integrin (αvβ3) receptor targeting peptide, cyclo-(Arg-Gly-Asp-D-Phe-Lys) (cRGfKD) and to the fluorescent probe sulfo-rhodamine B. The synthetic methodology presented herein is suitable for the large scale production of several novel heterobifunctionalized OEGs from readily available and inexpensive starting materials.

  在此，我们描述了一系列适用于叠氮-炔烃点击化学的异双功能寡（乙烯）醇（OEG）连接子 sequential synthesis，用于生物偶联化学应用。这些生物正交连接子的合成是通过将OEG中的一个羟基转化为炔烃或叠氮功能团，进而进行去对称化来完成的。OEG上的远端羟基则通过4-硝基苯基碳酸酯或美克酸酯（–OMs）基团进行活化。–OMs功能团作为一种有用的前驱体，用于形成包含不同高度反应性末端基团的多种异双功能化OEG连接子，例如：碘、–NH2、–SH和马来酰亚胺，这些基团与炔烃或叠氮功能团具有正交性。此外，炔烃和叠氮末端的OEG可通过采用Cu(I)催化的1,3-偶极环加成点击反应生成更大的离散聚（乙烯）醇（PEG）连接子（例如，PEG16和PEG24）。通过将整合素（αvβ3）受体靶向肽环（Arg-Gly-Asp-D-Phe-Lys）（cRGfKD）和荧光探针硫酸铑胺B附着于这些可点击的异双功能OEG中，证明了它们在生物偶联化学中的实用性。本文所呈现的合成方法适合于从易得且廉价的起始材料大规模生产多种新型异双功能化OEG。
• Substrates for o6-alkylguanina-dna alkyltransferase
  申请人：Kindermann Maik

  公开号：US20060024775A1

  公开（公告）日：2006-02-02

  The present invention relates to methods of transferring a label from novel substrates to O 6 -alkylguanine-DNA alkyltransferases (AGT) and O 6 -alkylguanine-DNA alkyltransferase fusion proteins, and to novel substrates suitable in such methods. Proteins of interest are incorporated into an AGT fusion protein, the AGT fusion protein is contacted with particular AGT substrates carrying a label, and the AGT fusion protein is detected and optionally further manipulated using the label in a system designed for recognising and/or handling the label. The particular AGT substrates used in the method of the invention are O 6 -substituted guanine derivatives or related nitrogen containing hydroxy-heterocycles and their sulfur analogs wherein the O 6 -substituent is an activated methyl derivative suitable for transfer from guanine or the corresponding heterocycle to AGT, and further carrying a label or a plurality of same or different labels. The invention relates also to the novel AGT substrates as such, to methods of manufacture of such novel substrates, and to intermediates useful in the synthesis of such novel AGT substrates.

  本发明涉及将标签从新型底物转移至O6-烷基鸟嘌呤-DNA烷基转移酶（AGT）和O6-烷基鸟嘌呤-DNA烷基转移酶融合蛋白质的方法，以及适用于这种方法的新型底物。感兴趣的蛋白质被并入AGT融合蛋白质中，AGT融合蛋白质与携带标签的特定AGT底物接触，并使用系统识别和/或处理标签来检测AGT融合蛋白质并可选地进一步操作。本发明中使用的特定AGT底物是O6取代鸟嘌呤衍生物或相关氮含杂环氢氧基化合物及其硫化物，其中O6取代基是适合从鸟嘌呤或相应杂环到AGT转移的活性甲基衍生物，并进一步携带一个标签或多个相同或不同的标签。本发明还涉及新型AGT底物本身，制造这种新型底物的方法，以及合成这种新型AGT底物的中间体。
• Substrates for O6-alkylguanina-DNA alkyltransferase
  申请人：Ecole Polytechnique Ferdeale de Lausanne

  公开号：US07799524B2

  公开（公告）日：2010-09-21

  The invention relates to compounds of formula 1 wherein R1-R2 is a guanine derivative; X is oxygen or sulfur; R3 is a heteroaromatic, unsaturated heterocyclyl or an alkynyl group with the double or triple bond connected to CH2; R4 is a linker; and L is a label, a plurality of same or different labels, a bond connecting R4 to R1 forming a cyclic substrate, or a further group —R3—CH2—X—R1-R2. The invention relates also to methods of manufacture of such novel AGT substrates, to intermediates useful in the synthesis of such AGT substrates, and to a method of transferring a label from such AGT substrates to O6-alkylguanine-DNA alkyltransferase (AGT) fusion proteins comprising proteins of interest.

  该发明涉及式1的化合物，其中R1-R2是鸟嘌呤衍生物；X是氧或硫；R3是杂环芳香基，不饱和杂环基或双键或三键连接到CH2的炔基；R4是连接基；L是标记，相同或不同的多个标记，连接R4到R1形成环状底物的键，或进一步的基团-R3-CH2-X-R1-R2。该发明还涉及制造此类新型AGT底物的方法，用于合成此类AGT底物的中间体以及将标记从此类AGT底物转移至包含感兴趣蛋白质的O6-烷基鸟嘌呤-DNA烷基转移酶（AGT）融合蛋白质的方法。