Strategies for Competitive Activity-Based Protein Profiling in Small Molecule Inhibitor Discovery and Characterization

  • Isr J Chem. 2023 Mar;63(3-4):e202200113. doi: 10.1002/ijch.202200113.
He Zhu  1  2  3 ,  Mona Sharafi  1  4 ,  Wei Pin Teh  1  4 ,  Ariana S Bratt  1  4 ,  Sara J Buhrlage  1  4  5 ,  Jarrod A Marto  1  2  3  5
Affiliations
  • 1. Department of Cancer Biology and the Linde Program, in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • 2. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • 3. Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA, USA.
  • 4. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
  • 5. Center for Emergent Drug Targets, Dana-Farber Cancer Institute, Boston, MA, USA.
PMID: 40718598 DOI: 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.

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