L-Arginine, N2,N6-bis[(1,1-dimethylethoxy)carbonyl]-L-lysyl-, methyl ester | 402496-24-6

• 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: L-Arginine, N2,N6-bis[(1,1-dimethylethoxy)carbonyl]-L-lysyl-, methyl ester
• 英文别名: Boc-Lys(Boc)-Arg-OMe
• CAS: 402496-24-6
• 化学式: C₂₃H₄₄N₆O₇
• 分子量: 516.638
• InChiKey: AISQBZOWJJZNHR-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  36.0
• 可旋转键数：
  13.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  193.96
• 氢给体数：
  6.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  L-Arginine, N2,N6-bis[(1,1-dimethylethoxy)carbonyl]-L-lysyl-, methyl ester 在 五氟苯酚 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 4.58h， 生成 DMQ-MA-Lys(DMQ-MA)-Arg-OMe
  参考文献：
  名称：

  摘要：

  This paper reports a continuing study of the use of short-chain peptides as carriers of a potential anti-tumour agent, namely 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). In an effort to carry out anti-cancer drug design, we have synthesized two new peptide-DMQ-MA conjugates: DMQ-MA-Lys(Cbz)-Arg-Arg-OMe and DMQ-MA-Lys(DMQ-MA)-Arg-OMe. These were synthesized by coupling protected amino acids using Pfp/N,N'-dicyclohexylcarbodiimide (Pfp = pentafluorophenol) in solution; the next conjugation was achieved by treatment with the pentafluorophenyl ester of DMQ-MA in dimethylformamide. We have investigated the DNA scission chemistry of these drugs, and the results show that they can cleave pBR322 DNA in concentrations as low as 5-40 muM without the addition of hydrogen peroxide or ultraviolet (UV) irradiation. The addition of a catalytic amount of ferrous ions has a significant enhancement on the DNA strand cleavage induced by the drugs: the cleavage degree increases with increasing time. Addition of hydroxyl radical scavengers such as dimethyl sulfoxide, glycerol, etc., significantly inhibits DNA strand cleavage. Oxidants with free-radical character are well known investigators of DNA damage. In order to explore the mechanism of DNA strand cleavage, we also investigated the reactive oxygen species. The active species produced by the drugs were studied using the Rhodamine B (Rhb) assay and electron paramagnetic resonance (EPR) spectroscopy. The results show fast production of the hydroxyl radical, which is trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and the characteristic signal of DMPO . OH (1 : 2 : 2 : 1) is recorded. DNA binding constants determined by the ethidium bromide assay are approximately 10(4) M-1. The results of this study show that the degree of DNA scission is not related to the binding constants, nor is it related to the hydroxyl radical intensity data solely, but rather to the ability of the drugs to generate various free radicals.

  DOI：

  10.1071/ch01063
• 作为产物：
  描述：

  (2S)-2-氨基-5-(二氨基亚甲基氨基)戊酸甲酯二盐酸盐 、 (S)-2,6-二叔丁氧羰基氨基己酸 在 五氟苯酚 、 N,N'-二环己基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.25h， 以76%的产率得到L-Arginine, N2,N6-bis[(1,1-dimethylethoxy)carbonyl]-L-lysyl-, methyl ester
  参考文献：
  名称：

  摘要：

  This paper reports a continuing study of the use of short-chain peptides as carriers of a potential anti-tumour agent, namely 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). In an effort to carry out anti-cancer drug design, we have synthesized two new peptide-DMQ-MA conjugates: DMQ-MA-Lys(Cbz)-Arg-Arg-OMe and DMQ-MA-Lys(DMQ-MA)-Arg-OMe. These were synthesized by coupling protected amino acids using Pfp/N,N'-dicyclohexylcarbodiimide (Pfp = pentafluorophenol) in solution; the next conjugation was achieved by treatment with the pentafluorophenyl ester of DMQ-MA in dimethylformamide. We have investigated the DNA scission chemistry of these drugs, and the results show that they can cleave pBR322 DNA in concentrations as low as 5-40 muM without the addition of hydrogen peroxide or ultraviolet (UV) irradiation. The addition of a catalytic amount of ferrous ions has a significant enhancement on the DNA strand cleavage induced by the drugs: the cleavage degree increases with increasing time. Addition of hydroxyl radical scavengers such as dimethyl sulfoxide, glycerol, etc., significantly inhibits DNA strand cleavage. Oxidants with free-radical character are well known investigators of DNA damage. In order to explore the mechanism of DNA strand cleavage, we also investigated the reactive oxygen species. The active species produced by the drugs were studied using the Rhodamine B (Rhb) assay and electron paramagnetic resonance (EPR) spectroscopy. The results show fast production of the hydroxyl radical, which is trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and the characteristic signal of DMPO . OH (1 : 2 : 2 : 1) is recorded. DNA binding constants determined by the ethidium bromide assay are approximately 10(4) M-1. The results of this study show that the degree of DNA scission is not related to the binding constants, nor is it related to the hydroxyl radical intensity data solely, but rather to the ability of the drugs to generate various free radicals.

  DOI：

  10.1071/ch01063