Detection of the prodrug-activating enzyme carboxypeptidase G2 activity with chemical exchange saturation transfer magnetic resonance.

Detection of the prodrug-activating enzyme carboxypeptidase G2 activity with chemical exchange saturation transfer magnetic resonance.
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DOI:
10.1007/s11307-013-0680-5
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发表时间:
2014-04
影响因子:
3.1
通讯作者:
Robinson, Simon P.
Robinson, Simon P.
中科院分区:
医学3区
文献类型:
--
作者:
Jamin, Yann;Eykyn, Thomas R.;Poon, Evon;Springer, Caroline J.;Robinson, Simon P.

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目的:探讨用化学交换饱和转移磁共振(CEST-MR)技术监测肿瘤基因治疗中使用的羧肽酶G2(CPG2)诱导谷氨酸释放的方法,以评价胺和酰胺质子与本体水的交换速率是否可以利用。研究了谷氨酸(胺)和CPG2底物3,5-二氟苯甲酰基-L-谷氨酸(3,5-DFBGlu)在11.7T、37℃和不同pH条件下的CEST性质。在表达CPG2的癌细胞提取液和纯化的CPG2溶液中检测CEST-MR监测CPG2介导的谷氨酸释放的能力。在含有3,5-DFBGlu的溶液中加入CPG2后,CEST效应显著且逐渐增强(+3ppm),并伴随着CPG2诱导的谷氨酸的时间依赖性释放。CEST-MR提供了体外CPG2活性的检测,并支持CEST-MRI的翻译以评估基于CPG2的体内基因治疗。
To evaluate if the differential exchange rates with bulk water between amine and amide protons can be exploited using chemical exchange saturation transfer magnetic resonance (CEST-MR) to monitor the release of glutamate induced by carboxypeptidase G2 (CPG2), an enzyme utilized in cancer gene therapy. The CEST properties of glutamate (amine) and the CPG2 substrate (amide), 3,5-difluorobenzoyl-L-glutamate (3,5-DFBGlu), were evaluated at 11.7T, 37°C and varying pH. The ability of CEST-MR to monitor CPG2-mediated release of glutamate was assessed in extracts of CPG2-expressing cancer cells and purified solution of CPG2. The addition of CPG2 to a solution containing 3,5-DFBGlu led to a marked and progressively increasing CEST effect (+3ppm), concomitant with the time-dependent release of glutamate induced by CPG2. CEST-MR affords the detection of CPG2 activity in vitro and supports the translation of CEST-MRI to assess CPG2-based gene therapy in vivo.
DOI: 10.1021/ja204701x
发表时间: 2011-10-19
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.
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影响因子: 3.3
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发表时间: 2011-04
影响因子: 3.3
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发表时间: 2012-01-22
期刊: Nature medicine
影响因子: 82.9
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DOI: 10.1002/nbm.1597
发表时间: 2011-05-01
期刊: NMR IN BIOMEDICINE
影响因子: 2.9
作者:
Jamin, Yann;Smyth, Lynette;Payne, Geoffrey S.
通讯作者: Payne, Geoffrey S.