This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Technical Research Project 1, Protease ActivitybasedProfiling (PABP), will focus on activitybasedproteomics. Chemical activity based probes(ABPs) will be devised and synthesized for thethree most abundant classes of proteases: cysteine,serine, and metallo. General probes will becomprised of reactive chemical moieties (epoxides, flurophosphonates, hydroxamates etc), linked togeneral peptide scaffold for recognition and selectivity and a variety of tags for detection oflabeled proteases. These probes allow direct analysis of protease activity and can be used for anumber of primary applications including: 1) direct profiling of protease activity in crude proteomes,intact cells, and even whole animals 2) direct biochemical isolation and identification of proteasetargets 3) fluorescence based cellular imaging to uncover the spatial and temporal regulation ofprotease activities and 4) small molecule screening of inhibitor libraries in complex proteomes toidentify novel, selective lead compounds to address protease function. The tools developed in this TRPwill serve to advance the rest of the projects in the Proteolysis Center and will be made freely availableto the Protease community at large
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