3-{4-[({2-[bis(pyridin-2-ylmethyl)amino]ethyl}carbamoyl)methyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl}propanoic acid

• 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: 3-{4-[({2-[bis(pyridin-2-ylmethyl)amino]ethyl}carbamoyl)methyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl}propanoic acid
• 英文别名: 2-[4-[2-[2-[Bis(pyridin-2-ylmethyl)amino]ethylamino]-2-oxoethyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid；2-[4-[2-[2-[bis(pyridin-2-ylmethyl)amino]ethylamino]-2-oxoethyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid
• 化学式: C₃₀H₄₄N₈O₇
• 分子量: 628.729
• InChiKey: BIORHOWZEMBOGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.6
• 重原子数：
  45
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  183
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  gadolinium(III) chloride 、 3-{4-[({2-[bis(pyridin-2-ylmethyl)amino]ethyl}carbamoyl)methyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl}propanoic acid 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Imaging Insulin Secretion from Mouse Pancreas by MRI Is Improved by Use of a Zinc-Responsive MRI Sensor with Lower Affinity for Zn²⁺ Ions

  摘要：

  It has been demonstrated that divalent zinc ions packaged with insulin in beta-cell granules can be detected by MRI during glucose-stimulated insulin secretion using a gadolinium-based Zn2+-sensitive agent. This study was designed to evaluate whether a simpler agent design having single Zn2+-sensing moieties but with variable Zn2+ binding affinities might also detect insulin secretion from the pancreas. Using an implanted MR-compatible window designed to hold the pancreas in a fixed position for imaging, we now demonstrate that focally intense "hot spots" can be detected in the tail of the pancreas using these agents after administration of glucose to stimulate insulin secretion. Histological staining of the same tissue, verified that the hot spots identified by imaging correspond to clusters of islets, perhaps reflecting first-responder islets that are most responsive to a sudden increase in glucose. A comparison of images obtained when using a high-affinity Zn2+ sensor versus a lower-affinity sensor showed that the lower-affinity sensors produced the best image contrast. An equilibrium model that considers all possible complexes formed between Zn2+, the GdL sensor, and HSA predicts that a GdL sensor with lower affinity for Zn2+ generates a lower background signal from endogenous Zn2+ prior to glucose-stimulated insulin secretion (GSIS) and that the weaker binding affinity agent is more responsive to a further increase in Zn2+ concentration near beta-cells after GSIS. These model predictions are consistent with the in vivo imaging observations.

  DOI：

  10.1021/jacs.8b07607
• 作为产物：
  描述：

  N,N-二(2-吡啶甲基)乙二胺 在 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 50.0h， 生成 3-{4-[({2-[bis(pyridin-2-ylmethyl)amino]ethyl}carbamoyl)methyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl}propanoic acid
  参考文献：
  名称：

  Towards understanding the design of dual-modal MR/fluorescent probes to sense zinc ions

  摘要：

  一系列新的钆配合物已经合成，用于测试设计双模探针的能力，这些探针可以在锌结合时显示荧光或弛豫率响应的变化。通过对探针参数的迭代更改，这些化合物揭示了成功成像锌离子所需的设计协议。

  DOI：

  10.1039/c4dt02981j

文献信息

• ZINC SENSORS FOR IN VIVO IMAGING OF BETA-CELL FUNCTION BY MRI
  申请人：The Board of Regents of the University of Texas System

  公开号：US20190031640A1

  公开（公告）日：2019-01-31

  In some aspects, the present disclosure provides gadolinium based sensors which may be used to image zinc ions in vivo. In some embodiments, the compounds show appropriate reactivity with zinc ions while maintaining high relaxivity to achieve improved background relative to other sensors.

  在某些方面，本公开提供了基于钆的传感器，可用于在体内成像锌离子。在某些实施例中，这些化合物与锌离子显示出适当的反应性，同时保持高弛豫度，以实现相对于其他传感器的改善背景。