This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Technical Research Project 1, Protease ActivitybasedProfiling (PABP), will focus on activitybased proteomics. Chemical activity based probes(ABPs) will be devised and synthesized for the three most abundant classes of proteases: cysteine,serine, and metallo. General probes will be comprised of reactive chemical moieties (epoxides, flurophosphonates, hydroxamates etc), linked to general peptide scaffold for recognition and selectivity and a variety of tags for detection of labeled proteases. These probes allow direct analysis of protease activity and can be used for a number 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 protease targets 3) fluorescence based cellular imaging to uncover the spatial and temporal regulation of protease activities and 4) small molecule screening of inhibitor libraries in complex proteomes to identify novel, selective lead compounds to address protease function. The tools developed in this TRP will serve to advance the rest of the projects in the Proteolysis Center and will be made freely available to the Protease community at larg
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