title: Designed glucopeptides mimetics of myelin protein epitopes as synthetic probes for the detection of autoantibodies, biomarkers of multiple sclerosis.
abstract: We previously reported that CSF114(Glc) detects diagnostic autoantibodies in multiple sclerosis sera. We report herein a bioinformatic analysis of myelin proteins and CSF114(Glc), which led to the identification of five sequences. These glucopeptides were synthesized and tested in enzymatic assays, showing a common minimal epitope. Starting from that, we designed an optimized sequence, SP077, showing a higher homology with both CSF114(Glc) and the five sequences selected using the bioinformatic approach. SP077 was synthesized and tested on 50 multiple sclerosis patients' sera, and was able to detect higher antibody titers as compared to CSF114(Glc). Finally, the conformational properties of SP077 were studied by NMR spectroscopy and structure calculations. Thus, the immunological activity of SP077 in the recognition of specific autoantibodies in multiple sclerosis patients' sera may be ascribed to both the optimized design of its epitopic region and the superior surface interacting properties of its C-terminal region.
authors.affiliation: Laboratory of Peptide and Protein Chemistry and Biology, Department of Chemistry Ugo Schiff, University of Florence, I-50019 Sesto Fiorentino, Italy.
authors.forename: Shashank
authors.initials: S
authors.lastname: Pandey
authors.forename: Maria C
authors.initials: MC
authors.lastname: Alcaro
authors.forename: Mario
authors.initials: M
authors.lastname: Scrima
authors.forename: Elisa
authors.initials: E
authors.lastname: Peroni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Paolini
authors.forename: Sara
authors.initials: S
authors.lastname: Di Marino
authors.forename: Francesca
authors.initials: F
authors.lastname: Barbetti
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Papini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Ursi
authors.forename: Paolo
authors.initials: P
authors.lastname: Rovero
mesh_terms: D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006020:Glycopeptides / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood* / Q000276:immunology; D009185:Myelin Proteins / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D006020:Glycopeptides; D009185:Myelin Proteins