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• W2625964143 abstract "Abstract The synthesis of a spin label based on PD168393, a covalent inhibitor of a major anticancer drug target, the epidermal growth factor receptor (EGFR), is reported. The label facilitates the analysis of the EGFR structure in solution by pulsed electron paramagnetic resonance (EPR) spectroscopy. For various EGFR constructs, including near‐full‐length EGFR, we determined defined distance distributions between the two spin labels bound to the ATP binding sites of the EGFR dimer. The distances are in excellent agreement with an asymmetric dimer of the EGFR. Based on crystal structures, this dimer had previously been proposed to reflect the active conformation of the receptor but structural data demonstrating its existence in solution have been lacking. More generally, our study provides proof‐of‐concept that inhibitor‐based spin labeling enables the convenient introduction of site‐specific spin labels into kinases for which covalent or tight‐binding small‐molecule modulators are available." @default.
• W2625964143 created "2017-06-23" @default.
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• W2625964143 date "2017-06-19" @default.
• W2625964143 modified "2023-09-30" @default.
• W2625964143 title "Studying the Conformation of a Receptor Tyrosine Kinase in Solution by Inhibitor-Based Spin Labeling" @default.
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• W2625964143 doi "https://doi.org/10.1002/anie.201703154" @default.
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