Activity-based protein profiling: new developments and directions in functional proteomics.

Proteomic screening has become increasingly insightful with the availability of novel analytical tools and technologies. Detailed analysis and integration of the profound datasets attained from comprehensive profiling studies are enabling researchers to dig deeper into the foundations of genomic and proteomic networks, towards a clearer understanding of the intricate cellular circuitries they manifest. The major difficulty often lies in correlating the patho/physiological state presented with the underlying biological mechanisms; therefore, identification of causal variants as therapeutic targets is extremely important. Herein, we will describe methods that address this challenge through activity-based protein profiling, which applies chemical probes to the comparison and monitoring of protein dynamics across complex proteomes. Over recent years such activity-based probes have been creatively augmented with applications in gel-based separations, microarrays and in vivo imaging. These developments offer a newfound ability to characterise and differentiate cells, tissues and proteomes through activity-dependent signatures; this has expanded the scope and impact of activity-based probes in biomedical research.