bis-5-hydroxytriptamide-DPTA | 875429-83-7

• 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: bis-5-hydroxytriptamide-DPTA
• 英文别名: bis-5HT-DPTA；2-[bis[2-[carboxymethyl-[2-[2-(5-hydroxy-1H-indol-3-yl)ethylamino]-2-oxoethyl]amino]ethyl]amino]acetic acid
• CAS: 875429-83-7
• 化学式: C₃₄H₄₃N₇O₁₀
• 分子量: 709.756
• InChiKey: IAPKPQYSUNETOT-UHFFFAOYSA-N

物化性质

• 沸点：
  1138.9±65.0 °C(Predicted)
• 密度：
  1.459±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5.6
• 重原子数：
  51
• 可旋转键数：
  22
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  252
• 氢给体数：
  9
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  bis-5-hydroxytriptamide-DPTA 、 氯化钆 以 水 为溶剂， 生成 2-[bis[2-[carboxylatomethyl-[2-[2-(5-hydroxy-1H-indol-3-yl)ethylamino]-2-oxoethyl]amino]ethyl]amino]acetate;gadolinium(3+)
  参考文献：
  名称：

  A paramagnetic contrast agent with myeloperoxidase-sensing properties

  摘要：

  髓过氧化物酶（MPO）是正常和病理状态下炎症反应的重要组成部分。为了实现 MPO 的无创成像这一最终目标，我们使用了二乙烯四胺五乙酸的钆螯合双（5-羟基色胺）衍生物（L1-Gd3+ 盐）作为酶活性的顺磁传感器。我们测试了 L1-Gd3+ 是否能有效还原髓过氧化物酶的氧化形式，该氧化形式是该酶还原过氧化氢的结果。我们预计，在 MPO/H2O2 激活后，L1-Gd3+ 不仅会寡聚，还会与介质中的其他大分子结合，整个过程会导致 T1 加权磁共振成像信号净增加。

  DOI：

  10.1039/b601540a
• 作为产物：
  描述：

  二亚乙基三胺五乙酸二酐 、 5-羟基色胺 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以87%的产率得到bis-5-hydroxytriptamide-DPTA
  参考文献：
  名称：

  A paramagnetic contrast agent with myeloperoxidase-sensing properties

  摘要：

  髓过氧化物酶（MPO）是正常和病理状态下炎症反应的重要组成部分。为了实现 MPO 的无创成像这一最终目标，我们使用了二乙烯四胺五乙酸的钆螯合双（5-羟基色胺）衍生物（L1-Gd3+ 盐）作为酶活性的顺磁传感器。我们测试了 L1-Gd3+ 是否能有效还原髓过氧化物酶的氧化形式，该氧化形式是该酶还原过氧化氢的结果。我们预计，在 MPO/H2O2 激活后，L1-Gd3+ 不仅会寡聚，还会与介质中的其他大分子结合，整个过程会导致 T1 加权磁共振成像信号净增加。

  DOI：

  10.1039/b601540a

文献信息

• DTPA-bisamide-Based MR Sensor Agents for Peroxidase Imaging
  作者：Manuel Querol、John W. Chen、Ralph Weissleder、Alexei Bogdanov

  DOI：10.1021/ol050208v

  日期：2005.4.1

  The synthesis and some properties of two novel DTPA-bisamides are reported. These derivatives were designed as enzyme-activated contrast agents (CA) for magnetic resonance imaging. Both derivatives bear tyramido or 5-hydroxytryptamido groups that could be oligomerized in situ in the presence of peroxidase/H2O2 pair resulting in a net increase in longitudinal (R1) relaxivity.
• 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.
• A paramagnetic contrast agent with myeloperoxidase-sensing properties
  作者：Manel Querol、John W. Chen、Alexei A. Bogdanov, Jr.

  DOI：10.1039/b601540a

  日期：——

  Myeloperoxidase (MPO) is an essential component of inflammatory response in norm and pathology. With an ultimate goal of non-invasive imaging of MPO we used a gadolinium-chelating bis(5-hydroxytrytamide) derivative of diethylenetetraamine pentaacetic acid (L1–Gd3+salt) as a paramagnetic sensor of enzymatic activity. We tested whether L1–Gd3+ is active in reducing the oxidized form of myeloperoxidase, generated as a result of hydrogen peroxide reduction by the enzyme. We expected that upon activation by MPO/H2O2 L1–Gd3+ would not only oligomerise but also bind to other macromolecules present in the media and that the overall process will give rise to a net T1-weighted MRI signal increase.

  髓过氧化物酶（MPO）是正常和病理状态下炎症反应的重要组成部分。为了实现 MPO 的无创成像这一最终目标，我们使用了二乙烯四胺五乙酸的钆螯合双（5-羟基色胺）衍生物（L1-Gd3+ 盐）作为酶活性的顺磁传感器。我们测试了 L1-Gd3+ 是否能有效还原髓过氧化物酶的氧化形式，该氧化形式是该酶还原过氧化氢的结果。我们预计，在 MPO/H2O2 激活后，L1-Gd3+ 不仅会寡聚，还会与介质中的其他大分子结合，整个过程会导致 T1 加权磁共振成像信号净增加。