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

Abstract

The epidermal growth factor receptor (EGFR) and HER2 are two important tyrosine kinases that play crucial roles in signal transduction pathways that regulate numerous cellular functions including proliferation, differentiation, migration, and angiogenesis. In the past 20 years, many proteomic methods have emerged as powerful methods to evaluate proteins in biological processes and human disease states. Among them, activity-based protein profiling (ABPP) is one useful approach for the functional analysis of proteins. In this study, a novel photoaffinity probe 11 was designed and synthesised to assess the target profiling of the reactive group in the photoaffinity probe 11. Biological evaluation was performed, and the results showed that the novel photoaffinity probe binds to EGFR and HER2 proteins and it hits targets by the reactive group.

Probes for Photoaffinity Labelling of Kinases

“…A) AfBPs based on dasatinib: 9 , [39] 10 , 11 , [40] 12 , [41] 13 , [30,42] 14 – 16 [28] . B) AfBPs based on imatinib: 17 , [30,42] 18–20 , [43] 21 , [39] and C) those with a quinazoline core: 22 , [30] 23 , [44] 24 , [45] and 25 [46] …”

Expanded Application of a Photoaffinity Probe to Study Epidermal Growth Factor Receptor Tyrosine Kinase with Functional Activity

“…For example, Shreder and colleagues developed a quinazoline-derived photoaffinity probe (AX7593) for EGFRs, 32 but a bulky fluorescent tag (TAMRA) was introduced in the molecule via a PEG linker. More recently, Zheng et al reported a new photoaffinity probe targeting EGFRs based on the scaffold of 4-benzothienyl amino quinazoline, 33 but the direct incorporation of a biotin tag limited its versatile application. Despite these initial efforts, there remains a need to develop a multifunctional probe to assess and visualize EGFR kinase activity with distinct analyses in (patho)physiological systems.…”