Discovery and Visualization of Uncharacterized Drug-Protein Adducts Using Mass Spectrometry.

ABSTRACT: Drugs are often metabolized to reactive intermediates that form protein adducts. Adducts can inhibit protein activity, elicit immune responses, and cause life-threatening adverse drug reactions. The masses of reactive metabolites are frequently unknown, rendering traditional mass spectrometry-based proteomics approaches incapable of adduct identification. Here, we present Magnum, an open-mass search algorithm optimized for adduct identification, and Limelight, a web-based data processing package for analysis and visualization of data from all existing algorithms. Limelight incorporates tools for sample comparisons and xenobiotic-adduct discovery. We validate our tools with three drug/protein combinations and apply our label-free workflow to identify novel xenobiotic-protein adducts in CYP3

SUBMITTER: Riffle M 

PROVIDER: S-EPMC8892443 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature