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I was reading this article and found this sentence:

KC group found that some cancer cells became resistant to Boehringer Ingelheim’s covalent TKI afatinib (Giotrif) due to the oxidation of its target cysteine in EGFR

What would be the chemical method to discover that especially the target cysteine is oxidized? Can it be done with NMR or spectroscopy?

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NMR could likely be used to characterize a bulk sample of the drug and identify the presence of cysteine residue oxidation products, but would not be of much use for establishing that cancer cells oxidize (inactivate) the drug, nor precisely how it was inactivated, given the tiny amounts of material involved. Maybe LC-MS could be used. Probably worth pulling up the original paper to see how they did the work.

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  • $\begingroup$ Thanks for reply. Sorry, I was too low on time to reply sooner. I skimmed through the cited articles and I wasn't able to find the original reference. They focused on finding specific probes to bind the oxidised cysteine residue in a small molecule and then mass spectrometry to analyse. In another article I found that "Tandem MS analysis encompassing all oxidizable residues (cysteine and methionine; 97% overall amino acid coverage) confirms that oxidation occurs exclusively at Cys797" so I guess that was the method of choice. ( ncbi.nlm.nih.gov/pmc/articles/PMC3890870 ) $\endgroup$ – mpribis Jun 13 '17 at 8:13

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