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A Chemical Probe for Dehydrobutyrine
Author(s) -
Chambers Kaitlin A.,
Abularrage Nile S.,
Hill Caitlin J.,
Khan Imran H.,
Scheck Rebecca A.
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202003631
Subject(s) - chemistry , nucleophile , phosphoserine , bioorthogonal chemistry , dehydroalanine , cysteine , biochemistry , combinatorial chemistry , amine gas treating , phosphine , enzyme , peptide , serine , organic chemistry , click chemistry , catalysis
Bacterial phosphothreonine lyases, or phospholyases, catalyze a unique post‐translational modification that introduces dehydrobutyrine (Dhb) or dehydroalanine (Dha) in place of phosphothreonine or phosphoserine residues, respectively. We report the use of a phospha‐Michael reaction to label proteins and peptides modified with Dha or Dhb. We demonstrate that a nucleophilic phosphine probe is able to modify Dhb‐containing proteins and peptides that were recalcitrant to reaction with thiol or amine nucleophiles under mild aqueous conditions. Furthermore, we used this reaction to detect multiple Dhb‐modified proteins in mammalian cell lysates, including histone H3, a previously unknown target of phospholyases. This method should prove useful for identifying new phospholyase targets, profiling the biomarkers of bacterial infection, and developing enzyme‐mediated strategies for bioorthogonal labeling in living cells.