American Journal of Pharmacogenomics

, Volume 4, Issue 6, pp 371–381 | Cite as

Activity-Based Protein Profiling

Applications to Biomarker Discovery, In Vivo Imaging and Drug Discovery
  • Alicia B. Berger
  • Phillip M. Vitorino
  • Matthew BogyoEmail author


The genomic revolution has created a wealth of information regarding the fundamental genetic code that defines the inner workings of a cell. However, it has become clear that analyzing genome sequences alone will not lead to new therapies to fight human disease. Rather, an understanding of protein function within the context of complex cellular networks will be required to facilitate the discovery of novel drug targets and, subsequently, new therapies directed against them.

The past ten years has seen a dramatic increase in technologies that allow large-scale, systems-based methods for analysis of global biological processes and disease states. In the field of proteomics, several well-established methods persist as a means to resolve and analyze complex mixtures of proteins derived from cells and tissues. However, the resolving power of these methods is often challenged by the diverse and dynamic nature of the proteome. The field of activity-based proteomics, or chemical proteomics, has been established in an attempt to focus proteomic efforts on subsets of physiologically important protein targets. This new approach to proteomics is centered around the use of small molecules termed activity-based probes (ABPs) as a means to tag, enrich, and isolate, distinct sets of proteins based on their enzymatic activity.

Chemical probes can be ‘tuned’ to react with defined enzymatic targets through the use of chemically reactive warhead groups, fused to selective binding elements that control their overall specificity. As a result, ABPs function as highly specific, mechanism-based reagents that provide a direct readout of enzymatic activity within complex proteomes. Modification of protein targets by an ABP facilitates their purification and isolation, thereby eliminating many of the confounding issues of dynamic range in protein abundance. In this review, we outline recent advances in the field of chemical proteomics. Specifically, we highlight how this technology can be applied to advance the fields of biomarker discovery, in vivo imaging, and small molecule screening and drug target discovery.


Epidermal Growth Factor Receptor Cysteine Protease Fluorescence Resonance Energy Transfer Fatty Acid Amide Hydrolase Epidermal Growth Factor Receptor Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was funded by a National Technology Centers for Networks and Pathways grant, NIH grant U54 RR020843 (awarded to Dr Bogyo). Dr Berger was funded by NHGRI trainiing grant 5T32HG00044.


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Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Alicia B. Berger
    • 1
  • Phillip M. Vitorino
    • 1
  • Matthew Bogyo
    • 1
    Email author
  1. 1.Department of PathologyStanford University School of MedicineStanfordUSA

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