Synthetic tools to illuminate matrix metalloproteinase and proteasome activities

Abstract

This thesis describes the design, synthesis and application of chemical tools for the activity-based protein profiling of proteases, with the main focus on matrix metalloproteinases (MMPs) and the proteasome. The use of photoaffinity labeling is described and the thesis starts with an extensive outline of the three most often used photoreactive groups and their application in (recently published) protein profiling studies. Targeting MMPs is performed by application of photoaffinity probes, while the proteasome is commonly targeted by so-called suicide inhibitors. The last experimental chapter deals with the creation of a novel chemoselective cleavable linker and its use in the pull-down of active proteasome subunits.