Functional imaging of proteases: recent advances in the design and application of substrate-based and activity-based probes.
Functional imaging of proteases: recent advances in the design and application of substrate-based and activity-based probes.
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DOI：
10.1016/j.cbpa.2011.10.012
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发表时间：
2011-12
影响因子：
7.8
通讯作者：
Bogyo, Matthew
中科院分区：
文献类型：
--
作者：
Edgington, Laura E.;Verdoes, Martijn;Bogyo, Matthew
蛋白酶是在蛋白质底物中切割肽键的酶。这个过程对于靶蛋白的调节周转很重要，但它也可以产生蛋白质片段，然后执行其他功能。由于过去几十年的蛋白酶研究已经证实，蛋白水解是正常生理和多种疾病相关条件下必不可少的调节过程，因此开发蛋白酶活性成像方法的兴趣越来越大。蛋白酶也被认为是为数不多的可药物类蛋白质之一，因此大量基于小分子的蛋白酶抑制剂已被报道。这些化合物可作为探针设计的起点，用于靶向活性蛋白酶的成像应用。目前，已经开发了几种荧光探针来观察活细胞甚至整个生物体中的蛋白酶活性。两种主要的蛋白酶探针利用肽/蛋白底物或共价抑制剂，当结合到活性蛋白酶靶点时产生荧光信号。本文综述了蛋白酶成像探针设计的一些最新进展。特别地，它强调了底物和活性探针的优点和缺点，以及它们在半胱氨酸蛋白酶成像中的应用，半胱氨酸蛋白酶是多种人类疾病的重要生物标志物。
Proteases are enzymes that cleave peptide bonds in protein substrates. This process can be important for regulated turnover of a target protein but it can also produce protein fragments that then perform other functions. Because the last few decades of protease research have confirmed that proteolysis is an essential regulatory process in both normal physiology and in multiple disease-associated conditions, there has been an increasing interest in developing methods to image protease activity. Proteases are also considered to be one of the few druggable classes of proteins and therefore a large number of small molecule based inhibitors of proteases have been reported. These compounds serve as a starting point for the design of probes that can be used to target active proteases for imaging applications. Currently, several classes of fluorescent probes have been developed to visualize protease activity in live cells and even whole organisms. The two primary classes of protease probes make use of either peptide/protein substrates or covalent inhibitors that produce a fluorescent signal when bound to an active protease target. This review outlines some of the most recent advances in the design of imaging probes for proteases. In particular, it highlights the strengths and weaknesses of both substrate- and activity- based probes and their applications for imaging cysteine proteases that are important biomarkers for multiple human diseases.
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影响因子：
3.7
作者：
Cavallo-Medved D;Rudy D;Blum G;Bogyo M;Caglic D;Sloane BF
通讯作者：
Sloane BF
影响因子：
3.7
作者：
Blum G;Weimer RM;Edgington LE;Adams W;Bogyo M
通讯作者：
Bogyo M
影响因子：
--
作者：
Greenbaum, D;Medzihradszky, KF;Bogyo, M
通讯作者：
Bogyo, M
影响因子：
2.8
作者：
Kaiser, Christina L.;Chapman, Brittany J.;Cotanche, Douglas A.
通讯作者：
Cotanche, Douglas A.
影响因子：
14.8
作者：
Blum, Galia;von Degenfeld, Georges;Bogyo, Matthew
通讯作者：
Bogyo, Matthew