Mass spectrometry; Peptide; Disulfide bonds; MALDI; ISD; Isomers
Abstract :
[en] Disulfide connectivity in peptides bearing at least two intramolecular disulfide bonds is highly important for the structure and the biological activity of the peptides. In that context, analytical strategies allowing a characterization of the cysteine pairing are of prime interest for chemists, biochemists, and biologists. For that purpose, this study evaluates the potential of MALDI in-source decay (ISD) for characterizing cysteine pairs through the systematic analysis of identical peptides bearing two disulfide bonds, but not the same cysteine connectivity. Three different matrices have been tested in positive and/or in negative mode (1,5-DAN, 2-AB and 2-AA). As MALDI-ISD is known to partially reduce disulfide bonds, the data analysis of this study rests firstly on the deconvolution of the isotope pattern of the parent ions. Moreover, data analysis is also based on the formed fragment ions and their signal intensities. Results from MS/MS-experiments (MALDI-ISD-MS/MS) constitute the last reference for data interpretation. Owing to the combined use of different ISD-promoting matrices, cysteine connectivity identification could be performed on the considered peptides.
Disciplines :
Chemistry
Author, co-author :
Massonnet, Philippe ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Haler, Jean ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Uper, Gregory; Commissariat à l'Energie Atomique (Saclay) - CEA > DRF > SIMOPRO, 91191, Gif sur Yvette, France
Smargiasso, Nicolas ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Mourier, Gilles; Commissariat à l'Energie Atomique (Saclay) - CEA > DRF > SIMOPRO, 91191, Gif sur Yvette, France
Gilles, Nicolas; Commissariat à l'Energie Atomique (Saclay) - CEA > DRF > SIMOPRO, 91191, Gif sur Yvette, France
Quinton, Loïc ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie biologique
De Pauw, Edwin ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Language :
English
Title :
Disulfide Connectivity Analysis of Peptides Bearing Two Intramolecular Disulfide Bonds Using MALDI In-Source Decay
Publication date :
2018
Journal title :
Journal of the American Society for Mass Spectrometry
FP7 - 278346 - VENOMICS - High-throughput peptidomics and transcriptomics of animal venoms for discovery of novel therapeutic peptides and innovative drug development
Funders :
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture CE - Commission Européenne
Lewis, R.J., Garcia, M.L.: Therapeutic potential of venom peptides. Nat. Rev. Drug Discov. 2, 790–802 (2003)
Craik, D.J., Daly, N.L., Bond, T., Waine, C.: Plant cyclotides: a unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif. J. Mol. Biol. 294, 1327–1336 (1999)
Lindholm, P., Goransson, U., Johansson, S., Claeson, P., Gullbo, J., Larsson, R., Bohlin, L., Backlund, A.: Cyclotides: a novel type of cytotoxic agents. Mol. Cancer Ther. 1, 365–369 (2002)
Ganz, T.: Defensins: antimicrobial peptides of innate immunity. Nat. Rev. Immunol. 3, 710–720 (2003)
Lehrer, R.I., Ganz, T.: Antimicrobial peptides in mammalian and insect host defence. Curr. Opin. Immunol. 11, 23–27 (1999)
Góngora-Benítez, M., Tulla-Puche, J., Albericio, F.: Multifaceted roles of disulfide bonds. peptides as therapeutics. Chem. Rev. 114, 901–926 (2013)
Gray, W.R.: Disulfide structures of highly bridged peptides: a new strategy for analysis. Protein Sci. 2, 1732–1748 (1993)
Thornton, J.M.: Disulphide bridges in globular proteins. J. Mol. Biol. 151, 261–287 (1981)
Raina, S., Missiakas, D.: Making and breaking disulfide bonds. Annu. Rev. Microbiol. 51, 179–202 (1997)
Betz, S.F.: Disulfide bonds and the stability of globular proteins. Protein Sci. 2, 1551–1558 (1993)
Khakshoor, O., Nowick, J.S.: Use of disulfide “staples” to stabilize β-sheet quaternary structure. Org. Lett. 11, 3000–3003 (2009)
Cashman, T.J., Linton, B.R.: β-sheet hydrogen bonding patterns in cystine peptides. Org. Lett. 9, 5457–5460 (2007)
Leduc, A.-M., Trent, J.O., Wittliff, J.L., Bramlett, K.S., Briggs, S.L., Chirgadze, N.Y., Wang, Y., Burris, T.P., Spatola, A.F.: Helix-stabilized cyclic peptides as selective inhibitors of steroid receptor-coactivator interactions. Proc. Natl. Acad. Sci. U. S. A. 100, 11273–11278 (2003)
Santiveri, C.M., León, E., Rico, M., Jiménez, M.A.: Context-dependence of the contribution of disulfide bonds to β-hairpin stability. Chem. – A Eur. J. 14, 488–499 (2008)
Bock, J.E., Gavenonis, J., Kritzer, J.A.: Getting in shape: controlling peptide bioactivity and bioavailability using conformational constraints, (2013)
Wu, Y., Wu, X., Yu, J., Zhu, X., Zhangsun, D., Luo, S.: Influence of disulfide connectivity on structure and bioactivity of α-conotoxin TxIA. Molecules. 19, 966–979 (2014)
Benham, C.J., Jafri, M.S.: Disulfide bonding patterns and protein topologies. Protein Sci. 2, 41–54 (1993)
Walewska, A., Skalicky, J.J., Davis, D.R., Zhang, M.-M., Lopez-Vera, E., Watkins, M., Han, T.S., Yoshikami, D., Olivera, B.M., Bulaj, G.: NMR-based mapping of disulfide bridges in cysteine-rich peptides: application to the μ-conotoxin SxIIIA. J. Am. Chem. Soc. 130, 14280–14286 (2008)
Mobli, M., King, G.F.: NMR methods for determining disulfide-bond connectivities. Toxicon. 56, 849–854 (2010)
Calvete, J.J., Schrader, M., Raida, M., McLane, M.A., Romero, A., Niewiarowski, S.: The disulphide bond pattern of bitistatin, a disintegrin isolated from the venom of the viper Bitis arietans. FEBS Lett. 416, 197–202 (1997)
Bauer, M., Sun, Y., Degenhardt, C., Kozikowski, B.: Assignment of all four disulfide bridges in echistatin. J. Protein Chem. 12, 759–764 (1993)
Durand, K.L., Ma, X., Plummer, C.E., Xia, Y.: Tandem mass spectrometry (MSn) of peptide disulfide regio-isomers via collision-induced dissociation: utility and limits in disulfide bond characterization. Int. J. Mass Spectrom. 343–344, 50–57 (2013)
Durand, K.L., Ma, X., Xia, Y.: Intra-molecular reactions between cysteine sulfinyl radical and a disulfide bond within peptide ions. Int. J. Mass Spectrom. 378, 246–254 (2015)
Massonnet, P., Upert, G., Smargiasso, N., Gilles, N., Quinton, L., De Pauw, E.: Combined use of ion mobility and collision-induced dissociation to investigate the opening of disulfide bridges by electron-transfer dissociation in peptides bearing two disulfide bonds. Anal. Chem. 87, 5240–5246 (2015)
Tan, L., Durand, K.L., Ma, X., Xia, Y.: Radical cascades in electron transfer dissociation (ETD)—implications for characterizing peptide disulfide regio-isomers. Analyst. (2013)
Fukuyama, Y., Iwamoto, S., Tanaka, K.: Rapid sequencing and disulfide mapping of peptides containing disulfide bonds by using 1,5-diaminonaphthalene as a reductive matrix. J. Mass Spectrom. 41, 191–201 (2006)
Demeure, K., Gabelica, V., De Pauw, E.A.: New advances in the understanding of the in-source decay fragmentation of peptides in MALDI-TOF-MS. J. Am. Soc. Mass Spectrom. 21, 1906–1917 (2010)
Asakawa, D.: Principles of hydrogen radical mediated peptide/protein fragmentation during matrix-assisted laser desorption/ionization mass spectrometry. Mass Spectrom. Rev. (2014)
Yang, H., Liu, N., Liu, S.: Determination of peptide and protein disulfide linkages by MALDI mass spectrometry. Top. Curr. Chem. 331, 79–116 (2013)
Quinton L., Demeure K., Dobson R., Gilles N., Gabelica V., De Pauw E.: New method for characterizing highly disulfide-bridged peptides in complex mixtures: application to toxin identification from crude venoms. (2007)
Volker Schnaible, Stephan Wefing, Anja Resemann, Detlev Suckau, Anne Bücker, Sybille Wolf-Kümmeth, Hoffmann, D.: Screening for disulfide bonds in proteins by MALDI in-source decay and LIFT-TOF/TOF-MS. (2002)
Hardouin, J.: Protein sequence information by matrix-assisted laser desorption/ionization in-source decay mass spectrometry. Mass Spectrom. Rev. 26, 672–682 (2007)
Massonnet, P., Haler, J.R.N.J.R.N., Upert, G., Degueldre, M., Morsa, D., Smargiasso, N., Mourier, G., Gilles, N., Quinton, L., De Pauw, E.: Ion mobility-mass spectrometry as a tool for the structural characterization of peptides bearing intramolecular disulfide bond(s). J. Am. Soc. Mass Spectrom. 27, 1637–1646 (2016)
Abdel Azzem, M., Yousef, U.S., Limosin, D., Pierre, G.: Electro-oxidative oligomerization of 1,5-diaminonaphthalene in acetonitrile medium. J. Electroanal. Chem. 417, 163–173 (1996)
Smargiasso, N., Quinton, L., De Pauw, E.: 2-Aminobenzamide and 2-aminobenzoic acid as new MALDI matrices inducing radical mediated in-source decay of peptides and proteins. J. Am. Soc. Mass Spectrom. 23, 469–474 (2012)
Asakawa, D., Smargiasso, N., Quinton, L., De Pauw, E.: Peptide backbone fragmentation initiated by side-chain loss at cysteine residue in matrix-assisted laser desorption/ionization in-source decay mass spectrometry, (2013)
