2-(3-butynyl)maleic acid anhydride | 1446684-83-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢呋喃
• 英文名称: 2-(3-butynyl)maleic acid anhydride
• 英文别名: 2-(3-butynyl)maleic anhydride；3-But-3-ynylfuran-2,5-dione；3-but-3-ynylfuran-2,5-dione
• CAS: 1446684-83-8
• 化学式: C₈H₆O₃
• 分子量: 150.134
• InChiKey: CISZOLUKUJBCPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-butynyl)maleic acid anhydride 在 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 aq. phosphate buffer 、 二氯甲烷 、 乙腈 为溶剂， 反应 28.0h， 生成 ((3aS,4R,10aS)-10,10-dihydroxy-2,6-diiminooctahydro-1H,8H-pyrrolo[1,2-c]purin-4-yl)methyl (2-(3-(3-(but-3-yn-1-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)ethyl)carbamate
  参考文献：
  名称：

  Maleimide Conjugates of Saxitoxin as Covalent Inhibitors of Voltage-Gated Sodium Channels

  摘要：

  (+)-萨克霉素是一种天然存在的胍类毒素，用作电压门控钠离子通道（Na(V)s）的强效、选择性和可逆抑制剂。通过全合成得到的这种毒素的修饰形式带有半胱氨酸反应的马来酰亚胺基团，发现这些修饰形式不可逆地抑制了在重组表达的野生型钠离子通道和海马神经细胞中钠离子的传导。我们的发现支持了一种共价蛋白质修饰机制，其中毒素结合到通道孔道先于马来酰亚胺对亲核氨基酸的烷基化。还包括生物正交反应基团的第二代马来酰亚胺毒素缀合物也被发现不可逆地阻断了通道功能；此类化合物在选择性标记钠离子通道（用于活细胞成像和/或蛋白质组学实验）的试剂方面具有潜在用途。

  DOI：

  10.1021/ja4019644
• 作为产物：
  描述：

  5-己炔-1-醇 在 草酰氯 、 吗啡啉盐酸盐 、 戴斯-马丁氧化剂 、 二甲基亚砜 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 生成 2-(3-butynyl)maleic acid anhydride
  参考文献：
  名称：

  Dual delivery of nucleic acids and PEGylated-bisphosphonates via calcium phosphate nanoparticles

  摘要：

  Despite many years of research and a few success stories with gene therapeutics, efficient and safe DNA delivery remains a major bottleneck for the clinical translation of gene-based therapies. Gene transfection with calcium phosphate (CaP) nanoparticles brings the advantages of low toxicity, high DNA entrapment efficiency and good endosomal escape properties. The macroscale aggregation of CaP nanoparticles can be easily prevented through surface coating with bisphosphonate conjugates. Bisphosphonates, such as alendronate, recently showed promising anticancer effects. However, their poor cellular permeability and preferential bone accumulation hamper their full application in chemotherapy. Here, we investigated the dual delivery of plasmid DNA and alendronate using CaP nanoparticles, with the goal to facilitate cellular internalization of both compounds and potentially achieve a combined pharmacological effect on the same or different cell lines. A pH-sensitive poly(ethyleneglycol)-alendronate conjugate was synthetized and used to formulate stable plasmid DNA-loaded CaP nano-particles. These particles displayed good transfection efficiency in cancer cells and a strong cytotoxic effect on macrophages. The in vivo transfection efficiency, however, remained low, calling for an improvement of the system, possibly with respect to the extent of particle uptake and their physical stability.

  DOI：

  10.1016/j.ejpb.2019.06.013

文献信息

• Maleimide Conjugates of Saxitoxin as Covalent Inhibitors of Voltage-Gated Sodium Channels
  作者：William H. Parsons、J. Du Bois

  DOI：10.1021/ja4019644

  日期：2013.7.24

  (+)-Saxitoxin, a naturally occurring guanidinium poison, functions as a potent, selective, and reversible inhibitor of voltage-gated sodium ion channels (Na(V)s). Modified forms of this toxin bearing cysteine-reactive maleimide groups are available through total synthesis and are found to irreversibly inhibit sodium ion conductance in recombinantly expressed wild-type sodium channels and in hippocampal nerve cells. Our findings support a mechanism for covalent protein modification in which toxin binding to the channel pore precedes maleimide alkylation of a nucleophilic amino acid. Second-generation maleimide-toxin conjugates, which include bioorthogonal reactive groups, are also found to block channel function irreversibly; such compounds have potential as reagents for selective labeling of Na(V)s for live cell imaging and/or proteomics experiments.

  (+)-萨克霉素是一种天然存在的胍类毒素，用作电压门控钠离子通道（Na(V)s）的强效、选择性和可逆抑制剂。通过全合成得到的这种毒素的修饰形式带有半胱氨酸反应的马来酰亚胺基团，发现这些修饰形式不可逆地抑制了在重组表达的野生型钠离子通道和海马神经细胞中钠离子的传导。我们的发现支持了一种共价蛋白质修饰机制，其中毒素结合到通道孔道先于马来酰亚胺对亲核氨基酸的烷基化。还包括生物正交反应基团的第二代马来酰亚胺毒素缀合物也被发现不可逆地阻断了通道功能；此类化合物在选择性标记钠离子通道（用于活细胞成像和/或蛋白质组学实验）的试剂方面具有潜在用途。
• Dual delivery of nucleic acids and PEGylated-bisphosphonates via calcium phosphate nanoparticles
  作者：Sofia Bisso、Simona Mura、Bastien Castagner、Patrick Couvreur、Jean-Christophe Leroux

  DOI：10.1016/j.ejpb.2019.06.013

  日期：2019.9

  Despite many years of research and a few success stories with gene therapeutics, efficient and safe DNA delivery remains a major bottleneck for the clinical translation of gene-based therapies. Gene transfection with calcium phosphate (CaP) nanoparticles brings the advantages of low toxicity, high DNA entrapment efficiency and good endosomal escape properties. The macroscale aggregation of CaP nanoparticles can be easily prevented through surface coating with bisphosphonate conjugates. Bisphosphonates, such as alendronate, recently showed promising anticancer effects. However, their poor cellular permeability and preferential bone accumulation hamper their full application in chemotherapy. Here, we investigated the dual delivery of plasmid DNA and alendronate using CaP nanoparticles, with the goal to facilitate cellular internalization of both compounds and potentially achieve a combined pharmacological effect on the same or different cell lines. A pH-sensitive poly(ethyleneglycol)-alendronate conjugate was synthetized and used to formulate stable plasmid DNA-loaded CaP nano-particles. These particles displayed good transfection efficiency in cancer cells and a strong cytotoxic effect on macrophages. The in vivo transfection efficiency, however, remained low, calling for an improvement of the system, possibly with respect to the extent of particle uptake and their physical stability.