(S)-3-(2-((S)-2-amino-5-guanidinopentanamido)acetamido)-4-(octyloxy)-4-oxobutanoic acid | 1148136-85-9

• 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: (S)-3-(2-((S)-2-amino-5-guanidinopentanamido)acetamido)-4-(octyloxy)-4-oxobutanoic acid
• CAS: 1148136-85-9
• 化学式: C₂₀H₃₈N₆O₆
• 分子量: 458.558
• InChiKey: MMDKWGMCLMUPRH-GJZGRUSLSA-N

物化性质

• 密度：
  1.30±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.44
• 重原子数：
  32.0
• 可旋转键数：
  18.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  209.72
• 氢给体数：
  7.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  4-benzyl 1-octyl L-aspartate 在 盐酸 、 5%-palladium/activated carbon 、 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 乙酸乙酯 为溶剂， 生成 (S)-3-(2-((S)-2-amino-5-guanidinopentanamido)acetamido)-4-(octyloxy)-4-oxobutanoic acid
  参考文献：
  名称：

  RGD-fatty alcohol-modified docetaxel liposomes improve tumor selectivity in vivo

  摘要：

  The tripeptide arginine-glycine-aspartate (RGD) was conjugated with various fatty alcohols to obtain RGDOC(n)H(2n) + 1 (n = 8, 10, 12, 14, 16, 18), which were incorporated into the bilayer of docetaxel liposomes to improve their tumor specificity. The fatty alcohols were accepted as linking groups to insert the tetrapeptide RGDX (X = amino acid) into the bilayer of liposomes. RGDX was previously shown to be a potent ligand to target tumor cell-surface integrin receptors, whereas RGD was not shown to have this ability. We hypothesized that RGD-fatty alcohol conjugates lacking the fourth amine X can guide liposomes to tumors without reducing their binding affinity to integrins. Antitumor activity, pharmacokinetics and biodistribution studies were evaluated in mice inoculated with S180 sarcoma. Compared with unmodified liposomes, RGD-fatty alcohol-modified liposomes successfully delivered significantly more docetaxel to tumors, which led to significant tumor weight loss and increased tumor docetaxel concentrations accompanied by reduced liver accumulation. Improved affinity of RGD-fatty alcohols to integrins was also confirmed on A375 cell model. Further comparisons among the tumor-targeting capacities of liposomes containing RGD-fatty alcohols, RGDF-fatty alcohols and RGDV-fatty acids demonstrated that RGD-fatty alcohols were as effective as the other two tetrapeptide derivatives. Therefore, a simplified tumor-targeting delivery system using RGD-fatty alcohols was developed. (C) 2014 Elsevier B. V. All rights reserved.

  DOI：

  10.1016/j.ijpharm.2014.04.001