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Generating cysteine-trypsin cleavage sites with 2-chloroacetamidine capping.

Samuel OforiHeta S DesaiFlowreen ShikwanaLisa M BoatnerEmil R Dominguez IiiJosé O CastellónKeriann M Backus
Published in: Chemical communications (Cambridge, England) (2024)
An electrophilic arginine mimetic, 2-chloroacetamidine (CAM), was deployed to enable trypsin-mediated proteolysis at cysteine residues and to enhance mass spectrometry-based proteomic detection of cysteine-containing peptides. Illustrating the value of the CAM-capping strategy, proteogenomic analysis using a two-stage false discovery rate (FDR) search revealed >50% enhanced coverage of missense variants, when compared to established workflows.
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