Complex proteomes activity-based probe

Activity-based protein profiling (ABPP) is a chemical proteomic strategy in which active-site-directed covalent probes are used to profile the functional states of enzymes in complex proteomes. Activity-based probes (ABPs) can distinguish active enzymes from their inactive zymogens or inhibitor-bound forms. They contain a reactive group intended to modify enzyme active sites covalently and a reporter group (typically rhodamine or biotin) that assists in detection and identification of protein targets. 

Salisbury CM, Cravatt BF (2007) Activity-based probes for proteomic profiling of histone deacetylase complexes. Proc Natl Acad Sci USA 104 1171-1176... 

Fig. 7.3-5 Inhibitor discovery by ABPP. The potency and selectivity of inhibitors can be profiled in parallel by performing competitive ABPP reactions in proteomes. Complex proteomes are treated with a reversible inhibitor library and an activity-based probe, and subsequently...

Although these probes show potent, heat-sensitive labeling profiles with purified tyrosine phosphatases, suggestive of specific active site modification, their use in complex proteomes was not reported [109]. Zhang and coworkers introduced a more specific class of tyrosine phosphatase probe [110]. This probe consists of an a-bromobenzylphosphonate moiety that acts as a tyrosine phosphate mimic and a mechanism-based inhibitor of tyrosine phosphatases. The chemistry of the probe mode of action is shown in Scheme 7. 

---