Comparative assessment of substrates and activity based probes as tools for non-invasive optical imaging of cysteine protease activity.
Comparative assessment of substrates and activity based probes as tools for non-invasive optical imaging of cysteine protease activity.
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DOI：
10.1371/journal.pone.0006374
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发表时间：
2009-07-28
期刊：
影响因子：
3.7
通讯作者：
Bogyo M
中科院分区：
文献类型：
--
作者：
Blum G;Weimer RM;Edgington LE;Adams W;Bogyo M
非侵入性光学成像领域的最新进展包括造影剂的开发，造影剂可以报告与疾病病理相关的酶靶点的活性。特别是，蛋白酶已被证明是开发用于癌症的光学传感器的理想目标。最近开发的蛋白酶活性对比剂包括小肽和大聚合物基猝灭荧光底物以及荧光标记活性探针（ABPs）。当底物通过蛋白酶加工产生荧光信号时，ABPs由于与活性位点催化残基形成永久共价键而保留在蛋白水解位点。这两种方法都有潜在的优点和缺点，但没有对底物和ABPs进行仔细的比较。在这里，我们提出了直接比较市售蛋白酶底物与最近描述的几种荧光ABPs在小鼠癌症模型中的结果。结果表明，与底物探针相比，荧光ABPs显示出更快速和选择性地被肿瘤吸收以及更亮的信号。这些数据表明，一旦结合到蛋白酶靶标上，组织摄取动力学的增加和探针的延长保留抵消了ABP信号放大的缺乏。此外，荧光ABPs可以用作成像试剂，具有与市售蛋白酶底物相似或更好的结果。
Recent advances in the field of non-invasive optical imaging have included the development of contrast agents that report on the activity of enzymatic targets associated with disease pathology. In particular, proteases have proven to be ideal targets for development of optical sensors for cancer. Recently developed contrast agents for protease activity include both small peptides and large polymer-based quenched fluorescent substrates as well as fluorescently labeled activity based probes (ABPs). While substrates produce a fluorescent signal as a result of processing by a protease, ABPs are retained at the site of proteolysis due to formation of a permanent covalent bond with the active site catalytic residue. Both methods have potential advantages and disadvantages yet a careful comparison of substrates and ABPs has not been performed. Here we present the results of a direct comparison of commercially available protease substrates with several recently described fluorescent ABPs in a mouse model of cancer. The results demonstrate that fluorescent ABPs show more rapid and selective uptake into tumors as well as overall brighter signals compared to substrate probes. These data suggest that the lack of signal amplification for an ABP is offset by the increased kinetics of tissue uptake and prolonged retention of the probes once bound to a protease target. Furthermore, fluorescent ABPs can be used as imaging reagents with similar or better results as the commercially available protease substrates.
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影响因子：
14.8
作者：
Blum, Galia;von Degenfeld, Georges;Bogyo, Matthew
通讯作者：
Bogyo, Matthew
影响因子：
4.1
作者：
McIntyre, JO;Fingleton, B;Matrisian, LM
通讯作者：
Matrisian, LM
基于活性的半胱氨酸胰蛋白酶选择性探针
影响因子：
16.6
作者：
Watzke, Anja;Kosec, Gregor;Wendt, K. Ulrich
通讯作者：
Wendt, K. Ulrich
影响因子：
16
作者：
Berger, Alicia B.;Witte, Martin D.;Bogyo, Matthew
通讯作者：
Bogyo, Matthew
影响因子：
7
作者：
Greenbaum, D;Baruch, A;Bogyo, M
通讯作者：
Bogyo, M