Improving Top-Down Sequence Coverage with Targeted Fragment Matching.

ABSTRACT: Top-down mass spectrometry (TDMS) of intact proteins and antibodies enables direct determination of truncations, sequence variants, post-translational modifications, and disulfides without the need for any proteolytic cleavage. While mass deconvolution of top-down tandem mass spectra is typically used to identify fragment masses for matching to candidate proteoforms, larger molecules such as monoclonal antibodies can produce many fragment ions, making spectral interpretation challenging. Here, we explore an alternative approach for proteoform spectral matching that is better suited for larger protein analysis. This workflow uses direct matching of theoretical proteoform isotopic distributions to TDMS spectra, avoiding drawbacks of mass deconvolution such as poor sensitivity and problems di

SUBMITTER: Robey MT 

PROVIDER: S-EPMC11623164 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature