Development of Bio-imaging Probes for Morbidity

发病率生物成像探针的开发

• 批准号: 11794026
• 负责人: NAGANO Tetsuo
• 金额: $ 6.34万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for University and Society Collaboration
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11794026/
• 关键词: probe; bio-imaging; MRI; zincion; neurotransfer; relaxation; fertilization; プローグ; 受精; 一酸化窒素

The MRI image is based upon the NMR signal from the protons of water, and the Signal intensity depends upon the water concentration and relaxation times. Nowadays, there is great interest in MRI contrast agents, which can improve the resolution of MR images. Gadolinium complexes are widely used as contrast agents for MRI.On the other hand, Zn^<2+> is the second most abundant heavy metal ion after iron in the human body. It is an essential component of many enzymes, transcription factors, and synaptic vesicles in excitatory nerve terminals and is present in serum at a concentration of 〜12 μM (total Zn^<2+>). Recently, Zn^<2+> has been reported to play important roles in regulating synaptic transmission and cell death. Therefore, imaging of chelatable Zn^<2+> in the extra- and intracellular environments or in tissues is of interest. A series of new diethylenetriaminepentaacetic acid (DTPA)-bisamide chelators has been prepared and characterized for application as Zn^<2+> sensors. We have designed and synthesized (GdL)^<2->, which contains a DTPA-bisamide moiety. The R_1 relaxivity of (GdL)^<2-> solution decreased monotonically on the addition of Zn^<2+>. Moreover, (GdL)^<2-> showed high selectivity for Zn^<2+> against Ca^<2+> and Mg^<2+>. These complexes should provide the basis for creating a superior Zn^<2+> sensitive MRI contrast agent and are excellent candidates for incorporation into sensors designed for selective detection of Zn^<2+> in biological applications.

MRI 图像基于来自水质子的 NMR 信号，信号强度取决于水浓度和弛豫时间。如今，人们对 MRI 造影剂产生了极大的兴趣，它可以提高 MR 图像的分辨率。钆配合物广泛用作MRI造影剂。另一方面，Zn^2+是人体内仅次于铁的第二丰富的重金属离子。它是兴奋性神经末梢中许多酶、转录因子和突触小泡的重要成分，并且在血清中的浓度约为12μM（总Zn 2+ ）。最近，据报道Zn 2+ 在调节突触传递和细胞死亡中发挥重要作用。因此，细胞外和细胞内环境或组织中的可螯合Zn 2+ 的成像是令人感兴趣的。一系列新型二亚乙基三胺五乙酸(DTPA)-双酰胺螯合剂已被制备和表征，可用作Zn^2+传感器。我们设计并合成了(GdL)^<2->，其含有DTPA-双酰胺部分。 (GdL)^2-溶液的R_1弛豫率随着Zn^2+的添加而单调降低。此外，(GdL) ^ 2- 对Zn ^ 2+ 表现出对Ca ^ 2+ 和Mg ^ 2+ 的高选择性。这些复合物应该为创建优异的Zn 2+ 敏感MRI造影剂提供基础，并且是结合到为在生物应用中选择性检测Zn 2+ 而设计的传感器中的优秀候选者。

项目成果

Noriyuki Sizuki: "Orthogonality of Calcium Concentration and Ability of 4,5-Diamino-fluoresein (DAF-2) to Detect NO"J. Biol. Chem.. 277. 47-49 (2002)

Noriyuki Sizuki：“钙浓度的正交性和 4,5-二氨基荧光素 (DAF-2) 检测 NO 的能力”J。

Motohiro Nishida: "Gi and Go as a Redox Sensor"J.Biol.Chem.. (in press).

Motohiro Nishida：“Gi 和 Go 作为氧化还原传感器”J.Biol.Chem..（印刷中）。

Tomoya Hirano: "Improved Fluorescent Probes for Zinc, ZnAFs, Suitable for Biological Applications"J. Am. Chem. Soc.. 124. 6555-6562 (2002)

Tomoya Hirano：“改进的锌、ZnAF 荧光探针，适合生物应用”J。

Tomoya Hirano, Kazuya Kikuchi, Yasuteru Urano and Tetsuo Nagano: "Improved Fluorescent Probes for Zinc, ZnAFs, Suitable for Biological Applications"J. Am. Chem. Soc.. 124. 6555-6562 (2002)

Tomoya Hirano、Kazuya Kikuchi、Yasuteru Urano 和 Tetsuo Nagano：“改进的锌、ZnAF 荧光探针，适合生物应用”J。

Sayaka Ueno: "Mossy Fiber Zn^<2+> Spillover Modulates Heterosynaptic N-methyl-D-aspartate Receptor Activity in Hippocampal CA3 Circuits"Cell Biology. 158. 215-220 (2002)

Sayaka Ueno：“苔藓纤维 Zn^<2 > 溢出调节海马 CA3 回路中的异突触 N-甲基-D-天冬氨酸受体活性”细胞生物学。