Activity-based proteomics: enzymatic activity profiling in complex proteomes.

Area of Science:

• Proteomics
• Biochemistry
• Chemical Biology

Background:

• Postgenomic era necessitates advanced techniques for global protein function analysis.
• Activity-based proteomics, utilizing active site-directed chemical probes, has emerged as a powerful tool.
• This approach significantly accelerates the functional annotation of proteins in complex biological samples.

Purpose of the Study:

• To review the design principles of activity-based probes for various enzyme classes.
• To highlight recent advancements, including in vivo applications and high-throughput screening technologies.
• To discuss the biological applications of activity-based probes in target and drug discovery.

Main Methods:

• Design and application of active site-directed chemical probes.
• Enzymatic activity profiling in complex biological mixtures.
• Detection using fluorescent, radioactive, or affinity tags coupled with proteomics techniques.

Main Results:

• Probes have been developed for diverse enzyme classes like serine hydrolases, cysteine proteases, and glycosidases.
• Recent developments include probes for in vivo proteome analysis and microarray-based screening.
• Activity-based probes are increasingly used for drug screening and target identification.

Conclusions:

• Activity-based proteomics is a rapidly advancing field with broad biological applications.
• The technology facilitates target and inhibitor discovery, with potential for drug screening.
• Future development requires addressing challenges to further enhance probe design and application.