Glu[Aca-BN(7–14)]2 | 1430102-08-1

• 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: Glu[Aca-BN(7–14)]2
• 英文别名: Glu[Aca-BN(7-14)]₂
• CAS: 1430102-08-1
• 化学式: C₁₀₃H₁₅₇N₂₉O₂₂S₂
• 分子量: 2217.69
• InChiKey: YLSZBTMRPAUZOB-RPKQXCPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  156.0
• 可旋转键数：
  74.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  811.12
• 氢给体数：
  27.0
• 氢受体数：
  27.0

反应信息

• 作为反应物：
  描述：

  sodium succinimidyl 6-(2-(2-sulfonatobenzaldehyde)hydrazono)nicotinate 、 Glu[Aca-BN(7–14)]2 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 168.0h， 以13%的产率得到HYNIC-Glu[Aca-BN(7-14)]₂
  参考文献：
  名称：

  Evaluation of a technetium-99m labeled bombesin homodimer for GRPR imaging in prostate cancer

  摘要：

  Multimerization of peptides can improve the binding characteristics of the tracer by increasing local ligand concentration and decreasing dissociation kinetics. In this study, a new bombesin homodimer was developed based on an epsilon-aminocaproic acid-bombesin(7-14) (Aca-bombesin(7-14)) fragment, which has been studied for targeting the gastrin-releasing peptide receptor (GRPR) in prostate cancer. The bombesin homodimer was conjugated to 6-hydrazinopyridine-3-carboxylic acid (HYNIC) and labeled with Tc-99m for SPECT imaging. The in vitro binding affinity to GRPR, cell uptake, internalization and efflux kinetics of the radiolabeled bombesin dimer were investigated in the GRPR-expressing human prostate cancer cell line PC-3. Biodistribution and the GRPR-targeting potential were evaluated in PC-3 tumor-bearing athymic nude mice. When compared with the bombesin monomer, the binding affinity of the bombesin dimer is about ten times lower. However, the Tc-99m labeled bombesin dimer showed a three times higher cellular uptake at 4 h after incubation, but similar internalization and efflux characters in vitro. Tumor uptake and in vivo pharmacokinetics in PC-3 tumor-bearing mice were comparable. The tumor was visible on the dynamic images in the first hour and could be clearly distinguished from non-targeted tissues on the static images after 4 h. The GRPR-targeting ability of the Tc-99m labeled bombesin dimer was proven in vitro and in vivo. This bombesin homodimer provides a good starting point for further studies on enhancing the tumor targeting activity of bombesin multimers.

  DOI：

  10.1007/s00726-012-1369-9