Targeting the Reactive Proteome: Recent Advances in Activity-Based Protein Profiling and Probe Design.

Area of Science:

• Chemical Biology
• Proteomics

Background:

• Activity-based protein profiling (ABPP) is a key chemical proteomics technique.
• It aids in profiling active amino acid residues and mapping functional proteins.
• ABPP is crucial for covalent drug development in biological systems.

Purpose of the Study:

• To review recent advancements in ABPP methodologies.
• To discuss the design of novel activity-based probes and photoaffinity labeling (PAL) probes.
• To highlight the implications of these advances for future chemical biology research.

Main Methods:

• Development of novel ABPP formats like TOP-ABPP and IsoTOP-ABPP.
• Design of chemical probes targeting specific amino acid residues (Cys, Lys, His).
• Integration of photoaffinity labeling (PAL) functionalities and cleavable linkers.

Main Results:

• Novel ABPP formats enable broader target identification and quantitative analysis.
• Advanced chemical probes offer selectivity for specific amino acid residues.
• Cleavable linkers enhance probe versatility and analytical workflows.

Conclusions:

• Recent methodological and probe design advances significantly expand ABPP capabilities.
• These innovations facilitate more comprehensive target identification and analysis in chemical biology.
• The described approaches hold promise for future drug discovery and biological studies.