Design and synthesis of a novel photoaffinity probe for labelling EGF receptor tyrosine kinases

Area of Science:

• Biochemistry and Molecular Biology
• Proteomics and Chemical Biology

Background:

• Epidermal growth factor receptor (EGFR) and HER2 are critical tyrosine kinases involved in cellular signaling pathways.
• These pathways regulate essential cellular functions such as proliferation, differentiation, migration, and angiogenesis.
• Proteomic methods, particularly activity-based protein profiling (ABPP), are vital for analyzing protein functions in biological processes and diseases.

Purpose of the Study:

• To design and synthesize a novel photoaffinity probe (compound 11) for target profiling.
• To evaluate the reactivity and specificity of the probe's reactive group.
• To assess the binding of the probe to key signaling proteins like EGFR and HER2.

Main Methods:

• Chemical synthesis of a novel photoaffinity probe (compound 11).
• Activity-based protein profiling (ABPP) techniques for functional protein analysis.
• Biological evaluation to determine probe binding and target engagement.

Main Results:

• The novel photoaffinity probe 11 was successfully synthesized.
• Biological evaluation confirmed that probe 11 binds to both EGFR and HER2 proteins.
• The study demonstrated that the probe engages its targets through its reactive group.

Conclusions:

• The developed photoaffinity probe is effective for identifying EGFR and HER2 as targets.
• This probe serves as a valuable tool for functional proteomic analysis of tyrosine kinases.
• The findings highlight the utility of ABPP in understanding protein interactions in cellular signaling.