Activity-based protein profiling (ABPP) is recognized as a powerful and versatile chemoproteomic technology in drug discovery. Central to ABPP is the use of activity-based probes to report the activity of specific enzymes or reactivity of amino acid types in complex biological systems. Over the last two decades, ABPP has facilitated the identification of new drug targets and discovery of lead compounds in human and infectious disease. Furthermore, as part of a sustained global effort to illuminate the druggable proteome, the repertoire of target classes addressable with activity-based probes has vastly expanded in recent years. Here, we provide an overview of ABPP and summarise the major technological advances with an emphasis on probe development.

基于活性的蛋白质分析 (ABPP) 被认为是药物发现中一种强大且用途广泛的化学蛋白质组学技术。ABPP 的核心是使用基于活性的探针来报告复杂生物系统中特定酶的活性或氨基酸类型的反应性。在过去的二十年里，ABPP 促进了新药靶点的识别和人类和传染病中先导化合物的发现。此外，作为阐明可成药蛋白质组的持续全球努力的一部分，近年来可使用基于活动的探针寻址的目标类别的曲目已大大扩展。在这里，我们概述了 ABPP 并总结了主要的技术进步，重点是探针的开发。