一种catalyCEST MRI对比剂,可以检测酶催化生成的共价键
Dina V Hingorani1, Edward A Randtke, Mark D Pagel
1Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85724-5024, USA.
Journal of the American Chemical Society
|April 23, 2013
概括
催化增强化学交换和转移 (CEST) MRI 使用一种新型的对比剂来检测转谷氨酶 (TGase) 活性. 这种方法可视化了酶催化共价键的形成,为分子成像提供了新的可能性.
科学领域:
- 生物医学成像技术 生物医学成像技术
- 磁共振成像是一种磁共振成像技术.
- 化学生物学 化学生物学
背景情况:
- 化学交换和转移 (CEST) MRI 使用专门的对比剂检测酶活性.
- 转胺酶 (TGase) 是一种形成共价键的酶,这种过程在当前的MRI技术中并不容易可视化.
研究的目的:
- 开发和验证一种用于检测TGase活动的新型CEST剂.
- 探索CESTMRI在可视化酶催化共价键形成方面的潜力.
主要方法:
- 一种新的CEST药物,Tm-DO3A-cadaverine,被设计用于准TGase.
- 通过TGase对该药物与专和模型的结合使用CESTMRI进行了研究.
- 修改的布洛赫方程用于分析CEST光谱和测量化学物质的汇率.
主要成果:
- 在TGase催化下,Tm-DO3A-cadaverine与白素的结合导致了新的CEST信号在-9.2 ppm下降,并在+4.6 ppm下降.
- 在TGase催化对模型的结合时观察到类似的CEST信号变化.
- CEST信号特征对序列和连接体构造敏感.
- 化学交换率的变化与共价键的形成相关.
结论:
- 开发的CEST剂通过MRI有效检测TGase活动.
- 通过监测化学交换速率的变化,CEST MRI可以通过监测化学交换速率的变化来可视化酶催化共价键形成.
- CEST剂对分子构造表现出敏感性,为更响应的分子成像剂铺平了道路.
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