title: The effect of post-translational and process-induced modifications on the multistage gas-phase fragmentation reactions of protonated peptides.
abstract: Significant effort has been extended in recent years toward the development and application of 'targeted' approaches for the identification, characterization and quantitative analysis of post-translational or process-induced protein modifications, based on the multistage tandem mass spectrometry (MS/MS and MS(3)) fragmentation reactions of their proteolytically derived peptide ions. Although these approaches have been successfully employed to date, the development of an improved understanding of the mechanisms and other factors (e.g., proton mobility, peptide conformation, product ion structures, etc.) that influence the multistage fragmentation reactions of modified peptide ions would facilitate further advances in the field. In this review, the important role of such mechanistic studies for rationalizing the effect of post-translational (e.g., phosphoserine- and phosphothreonine-containing peptides) and process-induced (e.g., oxidative modifications of methionine- and S-alkyl cysteine-containing peptides) protein modifications on the multistage collision induced dissociation gas-phase fragmentation reactions of proteolytically derived peptide ions are highlighted. Furthermore, recent efforts toward the development of chemical derivatization strategies for controlling and directing the gas-phase fragmentation reactions of protonated peptides toward the formation of analytically useful fragmentation pathways will be discussed, as well as the use of alternative dissociation techniques including electron capture dissociation (ECD) and electron transfer dissociation (ETD).
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Froelich
authors.forename: Gavin E
authors.initials: GE
authors.lastname: Reid
mesh_terms: D003545:Cysteine / Q000031:analogs & derivatives / Q000737:chemistry; D005740:Gases / Q000737:chemistry*; D013058:Mass Spectrometry; D008715:Methionine / Q000031:analogs & derivatives / Q000737:chemistry; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry*; D010766:Phosphorylation; D010768:Phosphoserine / Q000737:chemistry; D010769:Phosphothreonine / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D011522:Protons
chemical_list: D005740:Gases; D010446:Peptide Fragments; D011522:Protons; D010769:Phosphothreonine; D010768:Phosphoserine; D008715:Methionine; D003545:Cysteine; C013111:methionine sulfoxide