He Zhu; Mona Sharafi; Wei Pin Teh; Ariana S. Bratt; Sara J. Buhrlage; Jarrod A. Marto
Isr. J. Chem., 2023, 63, e202200113
https://doi.org/10.1002/ijch.202200113

Abstract

Since its introduction by Cravatt and colleagues in 1999, activity-based protein profiling (ABPP) has become widely utilized throughout academia, government, and industry laboratories to study enzymes spanning numerous gene families in a multitude of biological systems. As a variation of ABPP, competitive ABPP provides a powerful approach to characterize the binding behavior of small molecule probes and clinical drugs throughout the functional proteome. The power and flexibility of competitive ABPP are exemplified by a wide range of creative adaptions which increase assay throughput, enable diverse detection schemes, and support the implementation of this approach within a hybrid target-based screening platform. We review major developments in competitive ABPP through a compare-contrast format to provide a useful introduction to this enabling technology for scientists in chemical biology and drug discovery.