Abstract
The fragmentation of b3 ions derived from protonated Arg-Xxx-Asp-Ala-Ala (Xxx = Ala, Asp, Glu, Cys) and Arg-Xxx-Glu-Ala-Ala was investigated by electrospray ionization tandem mass spectrometry (MSn) with collision-induced dissociation. A particular ion, which is 1 Da less than b2 ion, is shown to be the c2-H2O ion. The mechanism for its formation involved the aspartic acid in the third position easily losing anhydride to form a c2 ion, which then lost water to form an eight-membered ring of azacyclooctane derivative under the participation of the guanidine of the N-terminal arginine. However, this phenomenon was not observed when the aspartic acid was replaced by glutamic acid. The Amber program was used to determine the conformation of the original c2 residue from the dynamic energy perspective, and then density functional theory-based calculations and changing N-terminal amino acid from arginine to phenylalanine supported this mechanism.
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Aebersold R, Goodlett DR (2001) Mass spectrometry in proteomics. Chem Rev 101:269–295
Azevedo RA (2002) Analysis of the aspartic acid metabolic pathway using mutant genes. Amino Acids 22:217–230
Balta B, Aviyente V, Lifshitz C (2003) Elimination of water from carboxyl group of GlyGlyH+. J Am Soc Mass Spectrom 14:1192–1203
Benjamin JB, Suhai S, Paizs B (2009) Proton-driven amide bond-cleavage pathways of gas-phase peptide ions lacking mobile protons. J Am Chem Soc 131:14057–14065
Bythell BJ, Csonka IP, Paizs B (2010) Gas-phase structure and fragmentation pathways of singly protonated peptides with N-terminal arginine. J Phys Chem B 114:15092–15105
Chai YF, Gan SF (2012) A mechanistic study of formation of radical anion from fragmentation of deprotonated N,2-diphenylacetamide derivatives in electrospray ionization tandem mass spectrometry. Acta Chim Sinica 70:1805–1811
Chai YF, Guo C, Jiang KZ (2012) C-alpha, C-beta and C-alpha N bond cleavage in the dissociation of protonated N-benzyllactams: dissociative proton transfer and intramolecular proton-transport catalysis. Org Biomol Chem 10:791–797
D’Aneillo S, Garcia-Fernandez J (2007) d-Aspartic acid and l-amino acids in the neural system of the amphioxus Branchiostoma lanceolatum. Amino Acids 32:21–26
Donger AR, Jones JL, Wysocki VH (1996) Influence of peptide composition, gas-phase basicity, and chemical modification on fragmentation efficiency: evidence for the mobile proton model. J Am Chem Soc 397:8365–8374
Fisher G, Lopez S, Pheterson K, Goff T, Philip I, Gaviria R, Lorenzo N, Tsesarskaia M (2007) Is there a correlation between age and d-aspartic acid in human knee cartilage. Amino Acids 32:27–30
Giuseppina B et al (2013) A practical route to long-chain non-natural α, ω-diamino acids. Amino Acids 44:435–441
Gu CG, Somogyi A, Wysocki VH (1999) Fragmentation of protonated oligopeptides XLDVLQ(X=L, H, K or R) by surface induced dissociation: addition evidence for the “mobile proton” model. Anal Chim Acta 397:247–256
Gu CG, Tsaprailis G, Breci L, Wysocki VH (2000) Selective gas-phase cleavage at the peptide bond C-terminal to aspartic acid in fixed-charge derivatives of asp-containing peptides. Anal Chem 72:5804–5813
Guo C, Wan JP, Hu N (2010) An experimental and computational investigation on the fragmentation behavior of enaminones in electrospray ionization mass spectrometry. J Mass Spectrom 45:1291–1298
Guo C, Jiang KZ, Yue L (2012) Intriguing roles of reactive intermediates in dissociation chemistry of N-phenylcinnamides. Org Biomol Chem 10:7070–7077
Guo C, Yue L, Guo MZ (2013) Elimination of benzene from protonated Nbenzylindoline: benzyl cation/proton transfer of direct proton transfer. J Am Soc Mass Spectrom 24:381–387
Harrison AG (1999) Linear free energy correlations in mass spectrometry. J Mass Spectrom 34:577–589
Harrison AG (2003) Fragmentation reactions of protonated peptides containing glutamine or glutamic acid. J Mass Spectrom 38:174–187
Harrison AG (2009) To b or not to b: the ongoing saga of peptide b ions. Mass Spectrom Rev 28:640–65438
Harrison AG (2012) Pathways for water loss from doubly protonated peptides containing serine or threonine. J Am Soc Mass Spectrom 23:116–123
Harrison AG, Csizmadia IG, Tang TH (2000) Structure and fragmentation of b2 ions in peptide mass spectra. J Am Soc Mass Spectrom 11:427–436
Herrmann KA, Wysocki VH, Vorpagel ER (2005) Computational investigation and hydrogen/deuterium exchange of the fixed charge derivative tris(2,4,6-trimethoxyphenyl) phosphonium: implications for the aspartic acid cleavage mechanism. J Am Soc Mass Spectrom 16:1067–1080
Huang Y, Wysocki VH, Tabb DL, Yates JR (2002) The influence of histidine on cleavage C-terminal to acidic residues in doubly protonated tryptic peptides. Int J Mass Spectrom 219:233–244
Jayaraman D, Atanu M, Khatija T, Chebrolu PR (2012) Benzimidazole conjugate of 1,1′-thiobis(2-naphthol) as switch-on fluorescence receptor for Ag+ and the complex as secondary recognition ensemble toward Cys, Asp, and Glu in aqueous methanolic solution: synthesis, characterization, ion and amino acid recognition, computational studies, and microscopy features. J Org Chem 77:371–378
Kyathanahalli C, Muralidhara (2010) d-Aspartic acid induced oxidative stress and mitochondrial dysfunctions in testis of prepubertal rats. Amino Acids. 38:817–827
Larsen MR, Roepstorff P (2000) Mass spectrometric identification of proteins and characterization of their post-translational modifications in proteome analysis. J Anal Chem 366:667–690
McCormack AL, Somogyi A, Dongre AR, Wysocki VH (1993) Fragmentation of protonated peptides: surface-induced dissociation in conjunction with a quantum-mechanical approach. Anal Chem 65:2859–2872
Molesworth SP, Van Stipdonk MJ (2010) Apparent inhibition by arginine of macrocyclic b ion formation from singly charged protonated peptides. J Am Soc Mass Spectrom 21:1322–1328
Morrison L, Somogyi A, Wysocki VH (2012) The influence glutamic acid in protonated b3–b2 formation form VGRIG and related analogs. Int J Mass Spectrom 325–327:139–149
Paizs B, Suhai S (1998) Comparative study of BSSR correction methods at DFT and MP2 levels of theory. J Comput Chem 19:575–584
Paizs B, Suhai S (2005) Fragmentation pathways of protonated peptides. Mass Spectrom Rev 24:508–548
Paizs B, Suhai S, Hargittai B (2002) Ab initio and MS/MS studies on protonated peptides containing basic and acidic amino acid residues: I. Solvated proton versus salt-bridged structures and the cleavage of the terminal amide bond of protonated RD-NH2. Int J Mass Spectrom 219:203–232
Pingitor F, Polce MJ, Wang P, Paizs B (2004) Intramolecular condensation reactions in protonated dipeptides: carbon monoxide, water, and ammonia losses in competition. J Am Soc Mass Spectrom 15:1025–1038
Polce MJ, Ren D, Wesdemiotis C (2000) Special feature: commentary-dissociation of the peptide bond in protonated peptides. J Mass Spectrom 35:1391–1398
Price WD, Schnier PD, Jockush RA, Williams ER (1996) Unimolecular reaction kinetics in the high-pressure limit without collisions. J Am Chem Soc 118:10640–10644
Rozman M (2007) Aspartic acid side chain effect-experimental and theoretical insight. J Am Soc Mass Spectrom 18:121–127
Sang WL, Hyun SK, Beauchamp JL (1998) Salt bridge chemistry applied to gas-phase peptide sequencing: selective fragmentation of sodiated gas-phase peptide ions adjacent to aspartic acid residues. J Am Chem Soc 120:3188–3195
Somogyi A, Harrison AG, Paizs B (2012) Using gas-phase guest-host chemistry to probe the structures of b ions of peptides. J Am Soc Mass Spectrom 23:2055–2058
Tsaprailis G, Nair H, Somogyi A, Wysocki VH (1999) Influence of secondary structure on the fragmentation of protonated peptides. J Am Chem Soc 121:5142–5154
Wang B, Shang JZ, Qin YJ, Guo XH (2011) Differentiation of a- or b-aspartic acid isomers in the heptapetides by the fragments of [M+Na]+ using ion trap tandem mass spectrometry. J Am Soc Mass Spectrom 22:1453–1462
Wysocki VH, Tsaprailis G, Smith LL (2000) Mobile and localized protons: a framework for understanding peptide dissociation. J Mass Spectrom 35:1399–1406
Yalcin T, Khouw C, Csizmadia IG (1995) Why are b ions stable species in peptide spectra? J Am Soc Mass Spectrom 6:1165–1174
You ZS, Wen YJ, Jiang KZ (2012) Fragmentation mechanism of product ions from protonated proline-containing tripeptides in electrospray ionization mass spectrometry. Chin Sci Bull 57:2051–2061
Yu W, Vath JE, Huberty MC, Martin SA (1993) 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 65:3015–3023
Zhang J, Chai YF (2012) Gas-phase smiles rearrangement of sulfonylurea herbicides in electrospray ionization mass spectrometry. Chin J Chem 30:2383–2388
Zhou Guisheng et al (2013) Hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry for highly rapid and sensitive analysis of underivatized amino acids in functional foods. Amino Acids 44:1293–1305
Acknowledgments
We wish to thank Professor Dr. Jianzhong Chen from College of Pharmaceutical Sciences, Zhejiang University, for his help of molecular dynamics simulation. We also gratefully acknowledge the financial support from the NSF of China (No. 21025207).
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The authors declare that they have no conflict of interest.
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Guo, M., Guo, C. & Pan, Y. Competitive formation of b2 and c2-H2O ions from b3 ions containing Asp residue during tandem mass spectrometry: the influence of neighboring Arg. Amino Acids 46, 1939–1946 (2014). https://doi.org/10.1007/s00726-014-1743-x
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DOI: https://doi.org/10.1007/s00726-014-1743-x