title: Mechanisms for the proton mobility-dependent gas-phase fragmentation reactions of S-alkyl cysteine sulfoxide-containing peptide ions.
abstract: Mechanisms for the gas-phase fragmentation reactions of singly and multiply protonated precursor ions of the model S-alkyl cysteine sulfoxide-containing peptides GAILCGAILK, GAILCGAILR, and VTMGHFCNFGK prepared by reaction with iodomethane, iodoacetamide, iodoacetic acid, acrylamide, or 4-vinylpyridine, followed by oxidation with hydrogen peroxide, as well as peptides obtained from an S-carboxyamidomethylated and oxidized tryptic digest of bovine serum albumin, have been examined using multistage tandem mass spectrometry, hydrogen/deuterium exchange and molecular orbital calculations (at the B3LYP/6-31 + G(d,p) level of theory). Consistent with previous reports, CID-MS/MS of the S-alkyl cysteine sulfoxide-containing peptide ions resulted in the dominant "non-sequence" neutral loss of an alkyl sulfenic acid (XSOH) from the modified cysteine side chains under conditions of low proton mobility, irrespective of the alkylating reagent employed. Dissociation of uniformly deuterated precursor ions of these model peptides determined that the loss of alkyl sulfenic acid in each case occurred via a "charge-remote" five-centered cis-1,2 elimination reaction to yield a dehydroalanine-containing product ion. Similarly, the charge state dependence to the mechanisms and product ion structures for the losses of CO(2), CO(2) + H(2)O and CO(2) + CH(2)O from S-carboxymethyl cysteine sulfoxide-containing peptides, and for the losses of CH(2)CHCONH(2) and CH(2)CHC(5)H(4)N, respectively, from S-amidoethyl and S-pyridylethyl cysteine sulfoxide-containing peptide ions have also been determined. The results from these studies indicate that both the proton mobility of the peptide precursor ion and the nature of the S-alkyl substituent have a significant influence on the abundances and charge states of the product ions resulting from the various competing fragmentation pathways.
authors: Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA.
authors: Jennifer M
authors: JM
authors: Froelich
authors: Gavin E
authors: GE
authors: Reid
mesh_terms: D003198:Computer Simulation; D003545:Cysteine / Q000737:chemistry*; D041961:Deuterium Exchange Measurement / Q000379:methods*; D007477:Ions; D008956:Models, Chemical; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D044367:Phase Transition; D011522:Protons; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013454:Sulfoxides / Q000737:chemistry*
chemical_list: D007477:Ions; D010455:Peptides; D011522:Protons; D013454:Sulfoxides; D003545:Cysteine
references: Mol Cell Proteomics. 2005 Mar;4(3):310-27
references: 15665377
references: J Am Soc Mass Spectrom. 2006 Dec;17(12):1631-42
references: 16935522
references: J Am Soc Mass Spectrom. 2007 Mar;18(3):493-501
references: 17126025
references: Anal Chem. 1996 Mar 1;68(5):850-8
references: 8779443
references: J Proteome Res. 2006 May;5(5):1252-60
references: 16674116
references: Nat Biotechnol. 2006 Oct;24(10):1285-92
references: 16964243
references: J Am Soc Mass Spectrom. 2001 Feb;12(2):228-32
references: 11212008
references: Rapid Commun Mass Spectrom. 2005;19(24):3626-32
references: 16287031
references: Anal Chem. 1998 Dec 15;70(24):5150-8
references: 9868912
references: Anal Chem. 2003 Nov 15;75(22):6251-64
references: 14616009
references: Proteomics. 2005 Jul;5(11):2761-8
references: 15966008
references: J Proteome Res. 2004 Jul-Aug;3(4):751-9
references: 15359728
references: Electrophoresis. 1999 Dec;20(18):3551-67
references: 10612281
references: Electrophoresis. 1996 May;17 (5):907-17
references: 8783016
references: J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89
references: 24226387
references: Electrophoresis. 2000 May;21(9):1707-32
references: 10870958
references: Proc Natl Acad Sci U S A. 1986 Sep;83(17):6233-7
references: 3462691
references: Electrophoresis. 1998 May;19(6):989-97
references: 9638945