Advances in Activity-Based Sensing Probes for Isoform-Selective Imaging of Enzymatic Activity.
Advances in Activity-Based Sensing Probes for Isoform-Selective Imaging of Enzymatic Activity.
复制标题
酶活性异构体选择性成像的活性传感探针研究进展。
DOI：
10.1002/anie.202003687
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发表时间：
2021-03-01
期刊：
影响因子：
--
通讯作者：
Chan J
中科院分区：
文献类型：
--
作者：
Gardner SH;Reinhardt CJ;Chan J
细胞通过严格的转录、翻译和翻译后调节来调节复杂的信号传导和代谢。在过去的几十年里，在监测转录和翻译方面取得了相当大的进展。直到最近，还没有普遍的方法来评估翻译后调控对酶活性的影响。基于活性的传感（ABS）已成为监测生命系统中小分子和酶活性的一种强大方法。ABS的初始实例被应用于测量一般的酶活性;然而，最近的重点是增加选择性以监测单个酶或同工型。需要最高程度的选择性来区分同种型，其中靶由于基因复制或选择性剪接而显示出显著的结构相似性。这篇综述突出了小分子，异构体选择性探针的关键例子，重点是异构体分化的相关性，设计策略，以实现选择性，并在基础生物学或临床应用。基于异构体选择性活性的探针的开发使得能够鉴定活系统内的酶活性。在这篇小综述中，我们突出了关键的例子，并讨论了亚型分化，设计策略和应用的相关性。
The cell regulates complicated signaling and metabolism through strict transcriptional, translational, and post-translational regulation. Considerable advances have been made for monitoring transcription and translation over the past few decades. Until recently, there have not been generalizable methods for assessing the effects of post-translational regulation on enzymatic activity. Activity-based sensing (ABS) has emerged as a powerful approach for monitoring small-molecule and enzymatic activities within living systems. Initial examples of ABS were applied for measuring general enzymatic activity; however, a recent focus has been on increasing selectivity to monitor a single enzyme or isoform. The highest degree of selectivity is required for differentiating between isoforms, where the targets display significant structural similarities as a result of a gene duplication or alternative splicing. This review highlights key examples of small-molecule, isoform-selective probes with a focus on the relevance of isoform differentiation, design strategies to achieve selectivity, and applications in basic biology or in the clinic. The development of isoform-selective activity-based probes enables the identification of enzymatic activity within living systems. Within this Minireview, we highlight key examples and discuss the relevance of isoform differentiation, design strategies, and applications.
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