Activity-based protein profiling: Recent advances in medicinal chemistry.

Area of Science:

• Chemical Proteomics
• Medicinal Chemistry
• Drug Discovery

Background:

• Activity-based protein profiling (ABPP) is an emerging chemical proteomic technique.
• It elucidates compound-protein interaction mechanisms, crucial for drug discovery.
• ABPP integrates organic synthesis, biochemistry, cell biology, biophysics, and bioinformatics.

Purpose of the Study:

• To review recent advancements and applications of ABPP in medicinal chemistry.
• To describe the design principles of activity-based probes (ABPs).
• To outline general workflows and diverse strategies within the ABPP approach.

Main Methods:

• Discussion of fundamental and advanced ABPP strategies.
• Detailed explanation of competitive and comparative ABPP.
• Overview of two-step ABPP, fluorescence polarization ABPP (FluoPol-ABPP), and visualization techniques using ABPs.

Main Results:

• The review summarizes the design and application of ABPs.
• Various ABPP strategies are discussed in the context of medicinal chemistry.
• The utility of ABPP in target identification, validation, and lead optimization is highlighted.

Conclusions:

• ABPP is a powerful and efficient technique in medicinal chemistry.
• It significantly aids in understanding drug action and optimizing therapeutic candidates.
• The review provides a comprehensive overview of ABPP's role in modern drug discovery.