Postproline proteases constitute a subset of serine proteases involved in the regulation of many signaling events and are emerging as promising therapeutic targets for prevalent diseases, such as diabetes and cancer. Therefore, monitoring their activity in different tissues and diverse physiological states would certainly facilitate the elucidation of their physiological role and the establishment of new therapeutic targets. Here, we have synthesized a dipeptidyl phosphonate activity-based probe ...
Postproline proteases constitute a subset of serine proteases involved in the regulation of many signaling events and are emerging as promising therapeutic targets for prevalent diseases, such as diabetes and cancer. Therefore, monitoring their activity in different tissues and diverse physiological states would certainly facilitate the elucidation of their physiological role and the establishment of new therapeutic targets. Here, we have synthesized a dipeptidyl phosphonate activity-based probe that has proved to be highly selective for a specific postproline protease, prolyl oligopeptidase (POP). Its high sensitivity allows the detection of the endogenous activity of POP both by in-gel analysis and mass spectrometry. The evidence provided by mass spectrometry for the high selectivity of the synthesized probe opens the possibility of using dipeptidyl phosphonates not only for activity-based profiling (ABP), but also for other ABP applications like substrate-based protease identification.
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