Line-Shifting Triarylmethyl Radicals for Imaging of Enzyme Activity Using Overhauser-Enhanced Magnetic Resonance Imaging: Application to Alkaline Phosphatase

被引：1
|
作者：
Velayutham, Murugesan [1 ,2 ]
Poncelet, Martin [2 ,3 ]
Enomoto, Ayano [4 ]
Huffman, Justin L. [2 ,3 ]
Pandya, Virat G. [2 ,3 ]
Ichikawa, Kazuhiro [4 ]
Khramtsov, Valery V. [1 ,2 ]
Driesschaert, Benoit [2 ,3 ,5 ]
机构：
[1] West Virginia Univ, Sch Med, Dept Biochem & Mol Med, Morgantown, WV 26506 USA
[2] West Virginia Univ, Vivo Multifunct Magnet Resonance Ctr, Robert C Byrd Hlth Sci Ctr, Morgantown, WV 26506 USA
[3] West Virginia Univ, Sch Pharm, Dept Pharmaceut Sci, Morgantown, WV 26506 USA
[4] Nagasaki Int Univ, Fac Pharmaceut Sci, Nagasaki 8593298, Japan
[5] West Virginia Univ, C Eugene Bennett Dept Chem, Morgantown, WV 26506 USA
来源：
CHEMICAL & BIOMEDICAL IMAGING | 2024年
关键词：
EPR; TAM radical; enzyme activity; alkaline phosphatase; OMRI; ELECTRON-PARAMAGNETIC-RESONANCE; LARGE-SCALE SYNTHESIS; IN-VIVO; TRIS(2,3,5,6-TETRATHIAARYL)METHYL CATIONS; EPR; OXYGEN; NITROXIDES; ACIDS; PH;
D O I：
10.1021/cbmi.4c00059
中图分类号：
O65 [分析化学];
学科分类号：
070302 ; 081704 ;
摘要：
Enzyme catalytic activities are critical biomarkers of tissue states under physiological and pathophysiological conditions. However, the direct measurement and imaging of enzyme activity in vivo remains extremely challenging. We report the synthesis and characterization of the first stable triarylmethyl (TAM) radical substrate of alkaline phosphatase (TAM-ALPs). The enzymatic dephosphorylation of TAM-ALPs results in a drastic change in its electron paramagnetic resonance (EPR) spectrum that can be used to image enzyme activity using EPR-based technologies. TAM-ALPs and their enzyme products were fully characterized using EPR and HPLC-MS techniques. A proof of concept of imaging enzyme activity using Overhauser-enhanced magnetic resonance imaging was demonstrated in vitro. This study clearly demonstrates the potential of EPR-based imaging technologies associated with TAM spin probes to map enzyme activity in vivo in future studies.
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页数：10
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