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Advanced Activity-Based Protein Profiling Application Strategies for Drug Development.

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  • 1Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Frontiers in Pharmacology
|April 25, 2018
PubMed
Summary

Activity-based protein profiling (ABPP) uses chemical probes to identify drug targets and their interactions. Advanced ABPP strategies like isoTOP-ABPP, fluoPol-ABPP, and qNIRF-ABPP enhance target identification and drug discovery.

Keywords:
ABPPdrug targetsfluoPol-ABPPisoTOP-ABPPqNIRF-ABPP

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Area of Science:

  • Chemical biology
  • Proteomics
  • Drug discovery

Background:

  • Identifying drug targets and mechanisms of action are key challenges in pharmaceutical development.
  • Chemical proteomic methods, including Activity-based Protein Profiling (ABPP), offer solutions by profiling targets within complex proteomes.
  • ABPP utilizes small-molecule chemical probes to elucidate compound-target interactions, identify protein targets, and map enzyme active sites.

Purpose of the Study:

  • This review details the Activity-based Protein Profiling (ABPP) workflow.
  • It explores advanced strategies for target identification and drug discovery using ABPP.
  • The focus is on small-molecule probe design and their application in validating compound-target interactions.

Main Methods:

  • Discussion of fundamental ABPP strategies, including click chemistry-ABPP and competitive assays.
  • Highlighting advanced techniques such as isoTOP-ABPP, fluoPol-ABPP, and qNIRF-ABPP.
  • Explaining the integration of ABPP with quantitative proteomics and high-throughput screening (HTS).

Main Results:

  • isoTOP-ABPP coupled with quantitative proteomics enables active site identification and proteome-wide amino acid profiling.
  • FluoPol-ABPP combined with HTS facilitates the discovery of novel compounds for substrate-free enzymes.
  • qNIRF-ABPP demonstrates utility in in vivo imaging applications.

Conclusions:

  • ABPP is a powerful chemical proteomic approach for target identification and drug discovery.
  • Advanced ABPP strategies offer enhanced capabilities for target validation, compound screening, and in vivo applications.
  • Continued development of ABPP methodologies promises to accelerate the drug development pipeline.