1 research outputs found
Leveraging Gas-Phase Fragmentation Pathways for Improved Identification and Selective Detection of Targets Modified by Covalent Probes
The
recent approval of covalent inhibitors for multiple clinical
indications has reignited enthusiasm for this class of drugs. As interest
in covalent drugs has increased, so too has the need for analytical
platforms that can leverage their mechanism-of-action to characterize
modified protein targets. Here we describe novel gas phase dissociation
pathways which yield predictable fragment ions during MS/MS of inhibitor-modified
peptides. We find that these dissociation pathways are common to numerous
cysteine-directed probes as well as the covalent drugs, Ibrutinib
and Neratinib. We leverage the predictable nature of these fragment
ions to improve the confidence of peptide sequence assignment in proteomic
analyses and explore their potential use in selective mass spectrometry-based
assays