Gas phase charge reduction for improved protein characterization by mass spectrometry

Heterogeneous mass spectra from large proteins, protein complexes, and their fragment ions, are often too congested to interpret, hence a significant analytical challenge in mass spectrometry. Overlap arising from broad charge-state distributions, structural heterogeneity, and post-translational modifications can obstruct accurate mass determination and protein characterization. To address these limitations, gas phase charge reduction strategies have emerged as a powerful approach to resolve spectral complexity and congestion. Gas phase ion-ion, ion-electron, and ion-neutral reactions are the primary mechanisms for charge reduction within the ion source or vacuum system of a mass spectrometer. This review highlights the above approaches utilized for two goals, intact mass measurement and enhanced tandem mass spectrometry characterization of proteins and protein complexes.