A catalyCEST MRI contrast agent that detects the enzyme-catalyzed creation of a covalent bond.
A catalyCEST MRI contrast agent that detects the enzyme-catalyzed creation of a covalent bond.
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DOI：
10.1021/ja400254e
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发表时间：
2013-05-01
影响因子：
15
通讯作者：
Pagel, Mark D.
中科院分区：
文献类型：
--
作者：
Hingorani, Dina V.;Randtke, Edward A.;Pagel, Mark D.
催化CEST MRI可以通过使用化学交换饱和转移（CEST）检测的造影剂来检测酶活性。一种CEST试剂Tm-DO3A-cadaverine被设计用于检测谷氨酰胺转酶（TGase）的催化活性，TGase在该试剂和谷氨酰胺氨基酸残基侧链之间形成共价键。TGase将tm - do3a -尸胺与白蛋白结合后，CEST出现在−9.2 ppm，这也导致CEST从+4.6 ppm的白蛋白下降。对模型多肽的研究显示，在gase催化的造影剂和多肽偶联后，类似的外观和可检测的CEST效应降低。这些CEST效应的MR频率和振幅取决于肽序列，这证明了CEST试剂对配体构象的敏感性，这可能被用来制造更灵敏的分子显像剂。通过将修正Bloch方程拟合到CEST光谱中，测量了底物和共轭产物的化学交换速率，结果表明，交换速率的变化也可以用于催化CEST MRI检测共价键的形成。
CatalyCEST MRI can detect enzyme activity by employing contrast agents that are detected through Chemical Exchange Saturation Transfer (CEST). A CEST agent, Tm-DO3A-cadaverine, has been designed to detect the catalytic activity of transglutaminase (TGase), which creates a covalent bond between the agent and the side chain of a glutamine amino acid residue. CEST appeared at −9.2 ppm after TGase conjugated Tm-DO3A-cadaverine to albumin, which also caused a decrease in CEST from albumin at +4.6 ppm. Studies with model peptides revealed similar appearances and decreases in detectable CEST effects following TGase-catalyzed conjugation of the contrast agent and peptide. The MR frequencies and amplitudes of these CEST effects were dependent on the peptide sequence, which demonstrated the sensitivity of CEST agents to ligand conformations that may be exploited to create more responsive molecular imaging agents. The chemical exchange rates of the substrates and conjugated products were measured by fitting modified Bloch equations to CEST spectra, which demonstrated that changes in exchange rates can also be used to detect the formation of a covalent bond by catalyCEST MRI.
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影响因子：
--
作者：
Li Y;Sheth VR;Liu G;Pagel MD
通讯作者：
Pagel MD
影响因子：
15
作者：
Liu, Guanshu;Liang, Yajie;Bar-Shir, Amnon;Chan, Kannie W. Y.;Galpoththawela, Chulani S.;Bernard, Segun M.;Tse, Terence;Yadav, Nirbhay N.;Walczak, Piotr;McMahon, Michael T.;Bulte, Jeff W. M.;van Zijl, Peter C. M.;Gilad, Assaf A.
通讯作者：
Gilad, Assaf A.
影响因子：
3.3
作者：
Liu, Guanshu;Li, Yuguo;Pagel, Mark D.
通讯作者：
Pagel, Mark D.
影响因子：
2.2
作者：
Ward, KM;Aletras, AH;Balaban, RS
通讯作者：
Balaban, RS
影响因子：
16.6
作者：
Chauvin, Thomas;Durand, Philippe;Toth, Eva
通讯作者：
Toth, Eva