Abstract
The fragmentation of the multiply charged peptides b-chain of bovine insulin and glucagon have been investigated under low energy collision induced dissociation (CID) conditions using an electrospray ion trap mass spectrometer. The influence of charge state, specific amino acids such as aspartate or proline, the location of basic sites, and the derivatization on the fragmentation behavior has been the focus of interest. As a basis for understanding the fragmentation process, the concept of the mobile proton was applied. A set of different derivatives was used to manipulate the sites of protonation of the peptides in order to control and improve the fragmentation behavior. These results can be applied for de novo sequencing, although the sequence-specific fragmentation processes have significant influence on the dissociation behavior of the peptides.
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Henzel, W. J.; Billeci, T. M.; Stults, J. S.; Wong, S.C.; Grimley, C.; Watanabe, C. Identifying Proteins from 2-Dimensional Gels by Molecular Mass Searching of Peptide Fragments in Protein Sequence Databases. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 5011–5015.
Billeci, T. M.; Stults, J. S. Tryptic Mapping of Recombinant Proteins by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. Anal. Chem. 1993, 65, 1709–1716.
Whittal, R. M.; Keller, B. O.; Li, L. Nanoliter Chemistry Combined with Mass Spectrometry for Peptide Mapping of Proteins from Single Mammalian Cell Lysates. Anal. Chem. 1998, 70(24), 5344–5347.
Pandey, A.; Mann, M. Proteomics to Study Genes and Genomes. Nature 2000, 405, 837–846.
Pitt, A. R. Application of Electrospray Mass Spectroemetry in Biology. Nat. Prod. Reports 1998, 59–72.
Marie, G.; Serani, L.; Laprévote, O. An On-Line Protein Digestion Device for Rapid Peptide Mapping by Electrospray Mass Spectrometry. Anal. Chem. 2000, 72(21), 5423–5430.
Roepstorff, P.; Fohlman, J. Proposal for a Common Nomenclature for Sequence Ions in Mass Spectrometry. J. Biomed. Mass Spectrom. 1984, 11, 601.
Smith, R. D.; Loo, J. A.; Edmonds, C. G.; Barinaga, C. J.; Udseth, H. R. Perspective: Analytical Biotechnology, New Developments in Biochemical Mass Spectrometry: Electrospray Ionization. Anal. Chem. 1990, 62, 882–899.
Knapp, D. R. Chemical Derivatization for Mass Spectrometry. Methods Enzymol. 1990, 193, 314–348.
Roth, K. D. W.; Huang, Z.-H.; Sadagopan, N.; Watson, J. T. Charge Derivatization of Peptides for Analysis by Mass Spectrometry. Mass Spectrom. Rev. 1998, 17, 255–274.
Huang, Z.-H.; Shen, T.; Wu, J.; Gage, D. A.; Watson, J. T. Protein Sequencing by Matrix-Assisted Laser Desorption Ionization-Postsource Decay-Mass Spectrometry Analysis of the N-Tris(2,4,6-trimethoxyphenyl) Phosphine-Acetylated Tryptic Digests. Anal. Biochem. 1999, 268, 305–317.
Liao, P.-C.; Huang, Z.-H.; Allison, J. Charge-Remote Fragmentation of Peptides Following Attachment of a Fixed Positive Charge: A Matrix-Assisted Laser Desorption/Ionization Post-source Decay Study. J. Am. Soc. Mass Spectrom. 1997, 8, 501–509.
Sadagopan, N.; Watson, J. Investigation of the Tris(trime-thoxyphenyl) Phosphonium Acetyl Charged Derivatives of Peptides by Electrospray Ionization Mass Spectrometry and Tandem Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2000, 11, 107–119.
Tang, X.-J.; Thibault, P.; Boyd, R. K. Fragmentation Reactions of Multiply Protonated Peptides and Implications for Sequencing by Tandem Mass Spectrometry with Low-Energy Collision-Induced Dissociation. Anal. Chem. 1993, 65, 2824–2834.
Jones, J. L.; Dongré, A. R.; Somogyi, Á.; Wysocki, V. H. Sequence Dependence of Peptide Fragmentation Efficiency Determined by Electrospray Ionization/Surface/Induced Dissociation Mass Spectrometry. J. Am. Chem. Soc. 1994, 116, 8368–8369.
Dongré, A. R.; Jones, J. L.; Somogyi, A.; Wysocki, V. H. Influence of Peptide Composition, Gas-Phase Basicity, and Chemical Modification on Fragmentation Efficiency: Evidence for the Mobile Proton Model. J. Am. Chem. Soc. 1996, 118, 8365–8374.
Gu, C.; Somogyi, A.; Wysocki, V. H.; Medzihradshky, K. F. Fragmentation of Protonated Oligopeptides XLDVLQ (X = L, H, K, or R) by Surface-Induced Dissociation: Additional Evidence for the Mobile Proton Model. Anal. Chim. Acta. 1999, 397, 247–256.
Downard, K. M.; Biemann, K. The Effect of Charge State and the Localization of Charge on the Collision-Induced Dissociation of Peptide Ions. J. Am. Soc. Mass Spectrom. 1994, 5, 966–975.
Downard, K. M.; Biemann, K. Charging Behavior of Highly-Basic Peptides During Electrospray Ionization. A Prediction for Protons. Int. J. Mass Spectrom. Ion Processes 1995, 148, 191–202.
Burlet, O.; Yang, C.-Y.; Gaskell, S. J. Influence of Cysteine to Cysteic Acid Oxidation on the Collision-Activated Decomposition of Protonated Peptides: Evidence for Intraionic Interactions. J. Am. Soc. Mass Spectrom. 1992, 3, 337–344.
Cox, K. A.; Gaskell, S. J.; Morris, M.; Whiting, A. Role of the Site of Protonation in the Low-Energy Decompositions of Gas-Phase Peptide Ions. J. Am. Soc. Mass Spectrom. 1996, 7, 522–531.
Keough, T.; Youngquist, R. S.; Lacey, M. P. A Method for High-Sensitivity Peptide Sequencing Using Postsource Decay Matrix-Assisted Laser Desorption Ionization Mass Spectrometry. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 7131–7136.
Bauer, M. D. Y.; Sun, Y.; Keough, T.; Lacey, M. P. Sequencing of Sulfonic Acid Derivatized Peptides by Electrospray Mass Spectrometry. Rapid Commun. Mass Spectrom. 2000, 14, 924–929.
Glocker, M. O.; Borchers, C.; Fiedler, W.; Suckau, D.; Przybylski, M. Molecular Characterization of Surface Topology in Protein Tertiary Structures by Amino-Acylation and Mass Spectrometric Peptide Mapping. Bioconj. Chem. 1994, 5, 583–590.
Keough, T.; Youngquist, R. S.; Lacey, M. P. A method for High-Sensitivity Peptide Sequencing Using Postsource Decay Matrix-Assisted Laser Desorption Ionization Mass Spectrometry. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 7131–7136.
Keough, T.; Lacey, M. P.; Fieno, M.; Grant, R. A.; Sun, Y.; Bauer, M. D.; Begley, K. B. Tandem Mass Spectrometry Methods for Definitive Protein Identification in Proteomics Research. Electrophoresis 2000, 21, 2252–2265.
Wagner, D. S.; Salari, A.; Gage, D. A.; Leykam, J.; Fetter, J.; Hollingsworth, R.; Watson, J. T. Derivatization of Peptides to Enhance Ionization Efficiency and Control Fragmentation During Analysis by FAB-MS. Biol. Mass Spectrom. 1991, 20, 419–425.
Yu, W.; Vath, J. E.; Huberty, M. C.; Martin, S. A. Identification of the Facile Gas-Phase Cleavage of the Asp-Pro and Asp-Xxx Peptide Bonds in Matrix-Assisted Laser Desorption Time-of-Flight Mass Spectrometry. Anal. Chem. 1993, 65, 3015–3023.
Gu, C.; Tsaprailis, G.; Breci, L.; Wysocki, V. H. Selective Gap-Phase Cleavage at the Peptide Bond Terminal to Aspartic Acid in Fixed-Charge Derivatives of Asp-Containing Peptides. Anal. Chem. 2000, 72, 5804–5813.
Schwartz, B. L.; Bursey, M. M. Some Proline Substituent Effects in the Tandem Mass Spectrum of Protonated Pentaalanine. Biol. Mass Spectrom. 1992, 21, 92–96.
Willard, B. B.; Kinter, M. Factors Affecting Amino Acid Sequence Information in CID-Spectra of Triply Charged Tryptic Peptides with an Internal Histidine. Proceedings of the ASMS Conference. June 2000, Long Beach, CA.
Bunk, D. M.; Macfarlane, R. D. Derivatization to Enhance Sequence-Specific Fragmentation of Peptides and Proteins. Int. J. Mass Spectrom. Ion Processes 1993, 126, 123–126.
Wagner, D. S.; Salari, A.; Gage, D. A.; Leykam, J.; Fetter, J.; Hollingsworth, R.; Watson, J. T. Derivatization of Peptides to Enhance Ionization Efficiency and Control Fragmentation During Analysis by FAB-MS. Biol. Mass Spectrom. 1991, 20, 419–425.
Miyagi, M.; Nakao, M.; Nakazawa, T.; Kato, I.; Tsunasawa, S. A Novel Derivatization Method with 5-Bromo-Nicotinic Acid N-Hydroxysuccinimide for Determination of the Amino Acid Sequences of Peptides. Rapid Commun. Mass Spectrom. 1998, 12, 603–608.
Keough, T.; Lacey, M. P.; Fieno, M.; Grant, R. A.; Sun, Y.; Bauer, M. D.; Begley, K. B. Tandem Mass Spectrometry Methods for Definitive Protein Identification in Proteomics Research. Electrophoresis 2000, 21, 2252–2265.
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Sonsmann, G., Römer, A. & Schomburg, D. Investigation of the influence of charge derivatization on the fragmentation of multiply protonated peptides. J Am Soc Mass Spectrom 13, 47–58 (2002). https://doi.org/10.1016/S1044-0305(01)00328-2
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DOI: https://doi.org/10.1016/S1044-0305(01)00328-2