N-Fmoc-(3-Fmoc-aminopropyl)glycine | 1259031-38-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-Fmoc-(3-Fmoc-aminopropyl)glycine
• 英文别名: N-Fmoc-N-(3-Fmoc-aminopropyl)glycine；2-[9H-fluoren-9-ylmethoxycarbonyl-[3-(9H-fluoren-9-ylmethoxycarbonylamino)propyl]amino]acetic acid
• CAS: 1259031-38-3
• 化学式: C₃₅H₃₂N₂O₆
• 分子量: 576.649
• InChiKey: GSMOHNPYVAQPLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl N-Fmoc-N-(3-Fmoc-aminopropyl)glycinate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以85.5%的产率得到N-Fmoc-(3-Fmoc-aminopropyl)glycine
  参考文献：
  名称：

  铂复合物/肽嵌合体作为潜在候选药物的合成和 DNA 相互作用

  摘要：

  抗癌药物顺铂的修饰和优化在选择性细胞靶向和 DNA 结合效率方面很受关注。有吸引力的方法包括铂配位球的修饰和顺铂结合部分的杂合分子的设计，包括肽基序。可以实现具有细胞穿透、导向或识别特性的肽。在这项研究中，研究了带正电荷的肽序列，其可能会诱导由 dsDNA 螺旋的电荷中和引起的 DNA 结构扭曲。带电肽的结合可能会增加 DNA 的灵活性，从而促进铂的结合。介绍了五种具有增强溶解性和潜在抗肿瘤活性的新型顺铂-肽杂交体的合成和 DNA 相互作用。丙烯二胺或双咪唑单元用作双齿铂配体，并在固相肽合成 (SPPS) 的最后延伸步骤中与肽序列偶联。琼脂糖和聚丙烯酰胺凝胶电泳、荧光嵌入和热紫外熔解研究都支持在由带正电荷的肽介导的反应中存在共价形成的铂 DNA 加合物。

  DOI：

  10.1002/ejoc.201000677

文献信息

• A Novel Platinum–Maurocalcine Conjugate Induces Apoptosis of Human Glioblastoma Cells by Acting through the ROS-ERK/AKT-p53 Pathway
  作者：Sonia Aroui、Lucie Dardevet、Wafa Ben Ajmia、Madryssa de Boisvilliers、Florian Perrin、Amel Laajimi、Ahcène Boumendjel、Abderraouf Kenani、Jean Marc Muller、Michel De Waard

  DOI：10.1021/acs.molpharmaceut.5b00531

  日期：2015.12.7

  Glioblastoma multiforme (GBM) is a highly malignant and aggressive primary brain tumor. In spite of an arsenal of therapeutic interventions, the prognosis of glioblastoma remains very poor. Cisplatin-based therapy is one of the most important chemotherapy treatments for GBM, although its efficacy is limited by drug resistance and undesirable side effects. In the present study, we designed a chimera molecule containing the platinum binding moiety MBL-III-7 (I) attached N-terminal to the sequence of D- maurocalcine (D-MCa), a protease-resistant and highly efficient cell-penetrating peptide (CPP) derived from the Tunisian chactid scorpion toxin, L-MCa. The concept behind this design is that MCa, through its cell retention properties, should reduce cell expulsion of the platinum complex and increase its efficiency. The anti-cancer properties of the synthesized platinum analogue Pt-MBL-III_7-D_MCa (Pt-1-DMCa) were assessed in human glioblastoma cells (U87) by assaying cell viability and apoptosis. The new molecule exhibited enhanced anti-cancer efficacy compared to cisplatin, especially at low doses. By inducing intracellular oxidative stress, Pt-1-DMCa potentiated platinum-induced DNA damage and led to enhanced p53 phosphorylation, followed by increased activation of both mitochondrial and death receptor pathways. Decreased phosphorylated AKT and ERK levels were associated with the apoptosis induced by the novel synthesized cisplatin analogue. Our results suggested that a chimera between platinum and a maurocalcine-derived CPP is a highly successful anti-cancer compound that works by targeting the intracellular redox system. Pt-1-DMCa is an interesting candidate for a preclinical assessment of platinum-based therapy in GBM treatments and possibly other cancer types.