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Selective identification and quantitative analysis of methionine containing peptides by charge derivatization and tandem mass spectrometry.
J Am Soc Mass Spectrom. 2005 Jul; 16(7):1131-50.JA

Abstract

To enable the development of a tandem mass spectrometry (MS/MS) based methodology for selective protein identification and differential quantitative analysis, a novel derivatization strategy is proposed, based on the formation of a "fixed-charge" sulfonium ion on the side-chain of a methionine amino acid residue contained within a protein or peptide of interest. The gas-phase fragmentation behavior of these side chain fixed charge sulfonium ion containing peptides is observed to result in exclusive loss of the derivatized side chain and the formation of a single characteristic product ion, independently of charge state or amino acid composition. Thus, fixed charge containing peptide ions may be selectively identified from complex mixtures, for example, by selective neutral loss scan mode MS/MS methods. Further structural interrogation of identified peptide ions may be achieved by subjecting the characteristic MS/MS product ion to multistage MS/MS (MS3) in a quadrupole ion trap mass spectrometer, or by energy resolved "pseudo" MS3 in a triple quadrupole mass spectrometer. The general principles underlying this fixed charge derivatization approach are demonstrated here by MS/MS, MS3 and "pseudo" MS3 analysis of side chain fixed-charge sulfonium ion derivatives of peptides containing methionine formed by reaction with phenacylbromide. Incorporation of "light" and "heavy" isotopically encoded labels into the fixed-charge derivatives facilitates the application of this method to the quantitative analysis of differential protein expression, via measurement of the relative abundances of the neutral loss product ions generated by dissociation of the light and heavy labeled peptide ions. This approach, termed "selective extraction of labeled entities by charge derivatization and tandem mass spectrometry" (SELECT), thereby offers the potential for significantly improved sensitivity and selectivity for the identification and quantitative analysis of peptides or proteins containing selected structural features, without requirement for extensive fractionation or otherwise enrichment from a complex mixture prior to analysis.

Authors+Show Affiliations

Joint Proteomics Laboratory, The Ludwig Institute for Cancer Research and The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. reid@chemistry.msu.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15923125

Citation

Reid, Gavin E., et al. "Selective Identification and Quantitative Analysis of Methionine Containing Peptides By Charge Derivatization and Tandem Mass Spectrometry." Journal of the American Society for Mass Spectrometry, vol. 16, no. 7, 2005, pp. 1131-50.
Reid GE, Roberts KD, Simpson RJ, et al. Selective identification and quantitative analysis of methionine containing peptides by charge derivatization and tandem mass spectrometry. J Am Soc Mass Spectrom. 2005;16(7):1131-50.
Reid, G. E., Roberts, K. D., Simpson, R. J., & O'Hair, R. A. (2005). Selective identification and quantitative analysis of methionine containing peptides by charge derivatization and tandem mass spectrometry. Journal of the American Society for Mass Spectrometry, 16(7), 1131-50.
Reid GE, et al. Selective Identification and Quantitative Analysis of Methionine Containing Peptides By Charge Derivatization and Tandem Mass Spectrometry. J Am Soc Mass Spectrom. 2005;16(7):1131-50. PubMed PMID: 15923125.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective identification and quantitative analysis of methionine containing peptides by charge derivatization and tandem mass spectrometry. AU - Reid,Gavin E, AU - Roberts,Kade D, AU - Simpson,Richard J, AU - O'Hair,Richard A J, PY - 2004/12/26/received PY - 2005/03/14/revised PY - 2005/03/16/accepted PY - 2005/6/1/pubmed PY - 2005/9/1/medline PY - 2005/6/1/entrez SP - 1131 EP - 50 JF - Journal of the American Society for Mass Spectrometry JO - J. Am. Soc. Mass Spectrom. VL - 16 IS - 7 N2 - To enable the development of a tandem mass spectrometry (MS/MS) based methodology for selective protein identification and differential quantitative analysis, a novel derivatization strategy is proposed, based on the formation of a "fixed-charge" sulfonium ion on the side-chain of a methionine amino acid residue contained within a protein or peptide of interest. The gas-phase fragmentation behavior of these side chain fixed charge sulfonium ion containing peptides is observed to result in exclusive loss of the derivatized side chain and the formation of a single characteristic product ion, independently of charge state or amino acid composition. Thus, fixed charge containing peptide ions may be selectively identified from complex mixtures, for example, by selective neutral loss scan mode MS/MS methods. Further structural interrogation of identified peptide ions may be achieved by subjecting the characteristic MS/MS product ion to multistage MS/MS (MS3) in a quadrupole ion trap mass spectrometer, or by energy resolved "pseudo" MS3 in a triple quadrupole mass spectrometer. The general principles underlying this fixed charge derivatization approach are demonstrated here by MS/MS, MS3 and "pseudo" MS3 analysis of side chain fixed-charge sulfonium ion derivatives of peptides containing methionine formed by reaction with phenacylbromide. Incorporation of "light" and "heavy" isotopically encoded labels into the fixed-charge derivatives facilitates the application of this method to the quantitative analysis of differential protein expression, via measurement of the relative abundances of the neutral loss product ions generated by dissociation of the light and heavy labeled peptide ions. This approach, termed "selective extraction of labeled entities by charge derivatization and tandem mass spectrometry" (SELECT), thereby offers the potential for significantly improved sensitivity and selectivity for the identification and quantitative analysis of peptides or proteins containing selected structural features, without requirement for extensive fractionation or otherwise enrichment from a complex mixture prior to analysis. SN - 1044-0305 UR - https://www.unboundmedicine.com/medline/citation/15923125/Selective_identification_and_quantitative_analysis_of_methionine_containing_peptides_by_charge_derivatization_and_tandem_mass_spectrometry_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1044-0305(05)00238-2 DB - PRIME DP - Unbound Medicine ER -