title: Selective Gas-Phase Oxidation and Localization of Alkylated Cysteine Residues in Polypeptide Ions via Ion/Ion Chemistry.
abstract: The thiol group in cysteine residues is susceptible to several post-translational modifications (PTMs), including prenylation, nitrosylation, palmitoylation, and the formation of disulfide bonds. Additionally, cysteine residues involved in disulfide bonds are commonly reduced and alkylated prior to mass spectrometric analysis. Several of these cysteine modifications, specifically S-alkyl modifications, are susceptible to gas-phase oxidation via selective ion/ion reactions with periodate anions. Multiply protonated peptides containing modified cysteine residues undergo complex formation upon ion/ion reaction with periodate anions. Activation of the ion/ion complexes results in oxygen transfer from the reagent to the modified sulfur residue to create a sulfoxide functionality. Further activation of the sulfoxide derivative yields abundant losses of the modification with the oxidized sulfur as a sulfenic acid (namely, XSOH) to generate a dehydroalanine residue. This loss immediately indicates the presence of an S-alkyl cysteine residue, and the mass of the loss can be used to easily deduce the type of modification. An additional step of activation can be used to localize the modification to a specific residue within the peptide. Selective cleavage to create c- and z-ions N-terminal to the dehydroalanine residue is often noted. As these types of ions are not typically observed upon collision-induced dissociation (CID), they can be used to immediately indicate where in the peptide the PTM was originally located.
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors.forename: Alice L
authors.initials: AL
authors.lastname: Pilo
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors.forename: Scott A
authors.initials: SA
authors.lastname: McLuckey
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000138:chemical synthesis; D000478:Alkylation; D003545:Cysteine / Q000737:chemistry*; D005740:Gases / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*; D010504:Periodic Acid / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D012451:Safrole / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D005740:Gases; D007477:Ions; D010455:Peptides; D010504:Periodic Acid; C015102:dehydroalanine; D003545:Cysteine; D000409:Alanine; D012451:Safrole; C005746:sulfoxide
keywords: S-alkylation; ion/ion reactions; oxidation; prenylation