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Activity-Based Probes

Activity-based probes (ABPs) are small molecules that show a tripartite structure. They consist of a reactive group, also called ‘warhead’, a linker or recognition element and a detection group suitable to either enrich the protein(s) of interest or detect them in solution or on a solid carrier (Figure 1).

The warhead often consists of an electrophilic reactive group for covalent binding to specific amino acids on the protein target(s). The linker group acts as a spacer preventing a steric clash between the warhead and the recognition element, but may also contain elements improving the selectivity of a probe. Additionally, the linker positions the reactive group for selective covalent targeting. In some cases, the linker and warhead may not be completely distinguishable. The detection group consist of a tag such as a click handle or biotin allowing high-affinity coupling to a solid support in order to enrich the protein for subsequent mass spectrometric analysis. Also fluorophores are used to visualise ABP-labelled proteins. In addition, radioisotopes may be coupled for gel-based visualisation or in vivo application e.g. in positron emission tomography. The tag may alter the properties of the probe including its cell penetrance or subcellular localisation.

Most ABPs are not designed to bind to a specific protein, but recently several potent and selective ABPs have been described.

The Chemical Probes Portal does not currently evaluate ABPs. activity-based-probes


  1. D. Conole, M. Mondal, J.D. Majmudar, E.W. Tate (2019) Front. Chem., DOI: 10.3389/fchem.2019.00876
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  3. S. Heinzlmeier, S. Müller (2021), Drug Discovery Today, DOI: 10.1016/j.drudis.2021.10.021