mono-5-hydroxytryptamide-DPTA | 1203928-12-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: mono-5-hydroxytryptamide-DPTA
• 英文别名: mono-5HT-DPTA；2-[2-[bis(carboxymethyl)amino]ethyl-[2-[carboxymethyl-[2-[2-(5-hydroxy-1H-indol-3-yl)ethylamino]-2-oxoethyl]amino]ethyl]amino]acetic acid
• CAS: 1203928-12-4
• 化学式: C₂₄H₃₃N₅O₁₀
• 分子量: 551.554
• InChiKey: HASGSBKCBOWTIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.9
• 重原子数：
  39
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  224
• 氢给体数：
  7
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  gadolinium(III) chloride hexahydrate 、 mono-5-hydroxytryptamide-DPTA 在 citric acid 作用下， 以 H₂O 为溶剂， 生成 mono-5-hydroxytryptamide-DPTA-Gd
  参考文献：
  名称：

  Activatable Magnetic Resonance Imaging Agents for Myeloperoxidase Sensing: Mechanism of Activation, Stability, and Toxicity

  摘要：

  Myeloperoxidase (MPO) is increasingly being recognized as an important factor in many inflammatory diseases, particularly cardiovascular and neurological diseases. MPO-specific imaging agents would thus be highly useful to diagnose early disease, monitor disease progression, and quantify treatment effects. This study reports in vitro and in vivo characterizations of the mechanism of interaction between MPO and paramagnetic enzyme substrates based on physical and biological measurements. We show that these agents are activated through a radical mechanism, which can combine to form oligomers and, in the presence of tyrosine-containing peptide, bind to proteins. We further identified two new imaging agents, which represent the near extremes in either oligomerization (mono-5HT-DTPA-Gd) or protein-binding in their activation mechanism (bis-o-dianisidine-DTPA-Gd). On the other hand, we found that the agent bis-5HT-DTPA-Gd utilizes both mechanisms when activated. These properties yield distinct in vivo pharmacokinetics profiles for each of these agents that may be exploited for different applications. Specificity studies show that only MPO, but not eosinophil peroxidase, can highly activate these agents, and that MPO activity as low as 0.005 U/mg of tissue can be detected. Gd kinetic lability and cytotoxicity studies further confirm stability of the Gd ion and low toxicity for the 5HT-based agents, suggesting that these agents are suitable for translational in vivo studies.

  DOI：

  10.1021/ja905274f
• 作为产物：
  描述：

  二亚乙基三胺五乙酸二酐 、 5-羟基色胺 在 吡啶 、 维生素 C 、 水 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 mono-5-hydroxytryptamide-DPTA
  参考文献：
  名称：

  Activatable Magnetic Resonance Imaging Agents for Myeloperoxidase Sensing: Mechanism of Activation, Stability, and Toxicity

  摘要：

  Myeloperoxidase (MPO) is increasingly being recognized as an important factor in many inflammatory diseases, particularly cardiovascular and neurological diseases. MPO-specific imaging agents would thus be highly useful to diagnose early disease, monitor disease progression, and quantify treatment effects. This study reports in vitro and in vivo characterizations of the mechanism of interaction between MPO and paramagnetic enzyme substrates based on physical and biological measurements. We show that these agents are activated through a radical mechanism, which can combine to form oligomers and, in the presence of tyrosine-containing peptide, bind to proteins. We further identified two new imaging agents, which represent the near extremes in either oligomerization (mono-5HT-DTPA-Gd) or protein-binding in their activation mechanism (bis-o-dianisidine-DTPA-Gd). On the other hand, we found that the agent bis-5HT-DTPA-Gd utilizes both mechanisms when activated. These properties yield distinct in vivo pharmacokinetics profiles for each of these agents that may be exploited for different applications. Specificity studies show that only MPO, but not eosinophil peroxidase, can highly activate these agents, and that MPO activity as low as 0.005 U/mg of tissue can be detected. Gd kinetic lability and cytotoxicity studies further confirm stability of the Gd ion and low toxicity for the 5HT-based agents, suggesting that these agents are suitable for translational in vivo studies.

  DOI：

  10.1021/ja905274f

文献信息

• Activatable Magnetic Resonance Imaging Agents for Myeloperoxidase Sensing: Mechanism of Activation, Stability, and Toxicity
  作者：Elisenda Rodríguez、Mark Nilges、Ralph Weissleder、John W. Chen

  DOI：10.1021/ja905274f

  日期：2010.1.13

  Myeloperoxidase (MPO) is increasingly being recognized as an important factor in many inflammatory diseases, particularly cardiovascular and neurological diseases. MPO-specific imaging agents would thus be highly useful to diagnose early disease, monitor disease progression, and quantify treatment effects. This study reports in vitro and in vivo characterizations of the mechanism of interaction between MPO and paramagnetic enzyme substrates based on physical and biological measurements. We show that these agents are activated through a radical mechanism, which can combine to form oligomers and, in the presence of tyrosine-containing peptide, bind to proteins. We further identified two new imaging agents, which represent the near extremes in either oligomerization (mono-5HT-DTPA-Gd) or protein-binding in their activation mechanism (bis-o-dianisidine-DTPA-Gd). On the other hand, we found that the agent bis-5HT-DTPA-Gd utilizes both mechanisms when activated. These properties yield distinct in vivo pharmacokinetics profiles for each of these agents that may be exploited for different applications. Specificity studies show that only MPO, but not eosinophil peroxidase, can highly activate these agents, and that MPO activity as low as 0.005 U/mg of tissue can be detected. Gd kinetic lability and cytotoxicity studies further confirm stability of the Gd ion and low toxicity for the 5HT-based agents, suggesting that these agents are suitable for translational in vivo studies.