γ-glutamyl phenylhydrazine | 13523-75-6

• 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: γ-glutamyl phenylhydrazine
• 英文别名: 2-Amino-5-oxo-5-(2-phenylhydrazinyl)pentanoic acid
• CAS: 13523-75-6
• 化学式: C₁₁H₁₅N₃O₃
• 分子量: 237.258
• InChiKey: PKAXVJHNWKFFPM-UHFFFAOYSA-N

物化性质

• 熔点：
  203 °C
• 沸点：
  414.0±45.0 °C(Predicted)
• 密度：
  1.321±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  104
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苯肼 、 DL-焦谷氨酸 生成 γ-glutamyl phenylhydrazine
  参考文献：
  名称：

  γ-Glutamyl transpeptidase-dependent mutagenicity and cytotoxicity of γ-glutamyl derivatives: A model for biochemical targeting of chemotherapeutic agents

  摘要：

  Many carcinomas in humans are rich in gamma-glutamyl transpeptidase (GGT). a plasma membrane enzyme that reacts with extracellular substrates. Thus, biochemical targeting of chemotherapeutic agents may be achieved by converting anticancer drugs into their gamma-glutamyl derivatives. Chemical conversion of phenylhydrazine (PH) and biochemical modification of daunomycin (DM) into their gamma-glutamyl derivatives gamma-glutamyl phenylhydrazine (GGPH) and gamma-glutamyl DM (GGDM) resulted in the abolishment of their mutagenicity and cytotoxicity, as judged by decreased viability and increased mutant yields in cultures of several Salmonella Ames strains. Commercial gamma-glutamyl-p-nitroanilide (GGPNA) was not toxic or mutagenic. Mutagenicity and/or cytotoxicity of these gamma-glutamyl derivatives were restored upon reaction with GGT, with concomitant release of PH, and p-nitroaniline (PNA). The GGT-dependent release of DM from GGDM was demonstrated by thin layer chromatography (TLC), spectral analysis, and specific mutagenicity. Mutagenicity and/or cytotoxicity of gamma-glutamyl derivatives increased in the presence of glycylglycine, a GGT activator, and decreased in the presence of serine-borate, a GGT inhibitor. GGDM retained considerable DNA binding capacity. Its inability to kill and mutagenize was due to altered transport properties. The results are compatible with the notion that gamma-glutamylation is a feasible method for biochemical targeting of drugs containing a primary amino group to GGT-rich tumors. Environ. Mol. Mutagen. 32:377-386 1998 (C) 1998 Wiley-Liss, Inc.

  DOI：

  10.1002/(sici)1098-2280(1998)32:4<377::aid-em12>3.0.co;2-1

文献信息

• γ-Glutamyl transpeptidase-dependent mutagenicity and cytotoxicity of γ-glutamyl derivatives: A model for biochemical targeting of chemotherapeutic agents
  作者：Ronit Keren、Avishay-Abraham Stark

  DOI：10.1002/(sici)1098-2280(1998)32:4<377::aid-em12>3.0.co;2-1

  日期：——

  Many carcinomas in humans are rich in gamma-glutamyl transpeptidase (GGT). a plasma membrane enzyme that reacts with extracellular substrates. Thus, biochemical targeting of chemotherapeutic agents may be achieved by converting anticancer drugs into their gamma-glutamyl derivatives. Chemical conversion of phenylhydrazine (PH) and biochemical modification of daunomycin (DM) into their gamma-glutamyl derivatives gamma-glutamyl phenylhydrazine (GGPH) and gamma-glutamyl DM (GGDM) resulted in the abolishment of their mutagenicity and cytotoxicity, as judged by decreased viability and increased mutant yields in cultures of several Salmonella Ames strains. Commercial gamma-glutamyl-p-nitroanilide (GGPNA) was not toxic or mutagenic. Mutagenicity and/or cytotoxicity of these gamma-glutamyl derivatives were restored upon reaction with GGT, with concomitant release of PH, and p-nitroaniline (PNA). The GGT-dependent release of DM from GGDM was demonstrated by thin layer chromatography (TLC), spectral analysis, and specific mutagenicity. Mutagenicity and/or cytotoxicity of gamma-glutamyl derivatives increased in the presence of glycylglycine, a GGT activator, and decreased in the presence of serine-borate, a GGT inhibitor. GGDM retained considerable DNA binding capacity. Its inability to kill and mutagenize was due to altered transport properties. The results are compatible with the notion that gamma-glutamylation is a feasible method for biochemical targeting of drugs containing a primary amino group to GGT-rich tumors. Environ. Mol. Mutagen. 32:377-386 1998 (C) 1998 Wiley-Liss, Inc.