title: Multi-Stage Mass Spectrometry Analysis of Sugar-Conjugated β-Turn Structures to be Used as Probes in Autoimmune Diseases.
abstract: Synthetic sugar-modified peptides were identified as antigenic probes in the context of autoimmune diseases. The aim of this work is to provide a mechanistic study on the fragmentation of different glycosylated analogs of a synthetic antigenic probe able to detect antibodies in a subpopulation of multiple sclerosis patients. In particular the N-glucosylated type I' β-turn peptide structure called CSF114(Glc) was used as a model to find signature fragmentations exploring the potential of multi-stage mass spectrometry by MALDI-LTQ Orbitrap. Here we compare the fragmentation of the glucosylated form of the synthetic peptide CSF114(Glc), bearing a glucose moiety on an asparagine residue, with less or non- immunoreactive forms, bearing different sugar-modifications, such as CSF114(GlcNAc), modified with a residue of N-acetylglucosamine, and CSF114[Lys(7)(1-deoxyfructopyranosyl)], this last one modified with a 1-deoxyfructopyranosyl moiety on a lysine at position 7. The analysis was set up using a synthetic compound specifically deuterated on the C-1 to compare its fragmentation with the fragmentation of the undeuterated form, and thus ascertain with confidence the presence on an Asn(Glc) within a peptide sequence. At the end of the study, our analysis led to the identification of signature neutral losses inside the sugar moieties to characterize the different types of glycosylation/glycation. The interest of this study lies in the possibility of applyimg this approach to the discovery of biomarkers and in the diagnosis of autoimmune diseases. Graphical Abstract <!-- [INSERT GRAPHICAL ABSTRACT TEXT HERE] -->.
authors.affiliation: Laboratory of Biological Mass Spectrometry and Proteomics, ESPCI ParisTech, PSL Research University, Paris, France. chiara.giangrande@espci.fr.|CNRS USR 3149 SMBP, Paris, France. chiara.giangrande@espci.fr.
authors.forename: Chiara
authors.initials: C
authors.lastname: Giangrande
authors.affiliation: Département de Chimie, École Normale Supérieure-PSL Research University, 24 rue Lhomond, 75005, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 place Jussieu, F-75005, Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Auberger
authors.affiliation: Laboratory of Peptide and Protein Chemistry and Biology - PeptLab, Sesto Fiorentino, Italy.|Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.|PeptLab@UCP Platform and Laboratory of Chemical Biology EA4505, University of Cergy-Pontoise, 5 mail Gay-Lussac, 95031, Cergy-Pontoise CEDEX, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Rentier
authors.affiliation: Laboratory of Peptide and Protein Chemistry and Biology - PeptLab, Sesto Fiorentino, Italy.|Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.|PeptLab@UCP Platform and Laboratory of Chemical Biology EA4505, University of Cergy-Pontoise, 5 mail Gay-Lussac, 95031, Cergy-Pontoise CEDEX, France.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Papini
authors.affiliation: Département de Chimie, École Normale Supérieure-PSL Research University, 24 rue Lhomond, 75005, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 place Jussieu, F-75005, Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Mallet
authors.affiliation: Département de Chimie, École Normale Supérieure-PSL Research University, 24 rue Lhomond, 75005, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 place Jussieu, F-75005, Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.
authors.forename: Solange
authors.initials: S
authors.lastname: Lavielle
authors.affiliation: Laboratory of Biological Mass Spectrometry and Proteomics, ESPCI ParisTech, PSL Research University, Paris, France.|CNRS USR 3149 SMBP, Paris, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Vinh
mesh_terms: D000906:Antibodies / Q000032:analysis; D006020:Glycopeptides / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D015335:Molecular Probes / Q000737:chemistry*; D009103:Multiple Sclerosis / Q000175:diagnosis*; D000072757:Protein Conformation, beta-Strand; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D000906:Antibodies; D006020:Glycopeptides; D015335:Molecular Probes
keywords: Autoimmune diseases; CID fragmentation; Glycosylation; Mass spectrometry; β-Turn structures