Date: 26 Oct 2011

Photoaffinity Labeling in Activity-Based Protein Profiling

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Activity-based protein profiling has come to the fore in recent years as a powerful strategy for studying enzyme activities in their natural surroundings. Substrate analogs that bind covalently and irreversibly to an enzyme active site and that are equipped with an identification or affinity tag can be used to unearth new enzyme activities, to establish whether and at what subcellular location the enzymes are active, and to study the inhibitory effects of small compounds. A specific class of activity-based protein probes includes those that employ a photo-activatable group to create the covalent bond. Such probes are targeted to those enzymes that do not employ a catalytic nucleophile that is part of the polypeptide backbone. An overview of the various photo-activatable groups that are available to chemical biology researchers is presented, with a focus on their (photo)chemistry and their application in various research fields. A number of comparative studies are described in which the efficiency of various photo-activatable groups are compared.