Posttranslationally modified peptides efficiently mimicking neoantigens: a challenge for theragnostics of autoimmune diseases.
We report the design, synthesis, and immunological evaluation of a series of glycopeptide analogues of the previously described antigenic probe CSF114(Glc), with the aim of understanding the importance of N-glycosylation on Asn residue in multiple sclerosis antibody recognition. The glucopeptide, characterized by a β-turn conformation which is fundamental for a correct presentation of the epitope, has been modified by introducing various natural glycoamino acids in position 7. The new glycopeptides were evaluated by measuring the IgG and IgM antibody titer in multiple sclerosis patients' and normal blood donors' sera. Moreover, we achieved the efficient synthetic strategy of new Asn derivative bearing N-acetylneuraminic acid (Neu5Ac), linked by an N-glycosidic bond, on the side chain of the Asn residue orthogonally protected for Fmoc/tBu SPPS.
Nuti
Francesca
F
Laboratory of Peptide and Protein Chemistry and Biology, Polo Scientifico e Tecnologico, University of Florence, Via della Lastruccia 3/13, I-50019 Sesto Fiorentino (FI), Italy.
Peroni
Elisa
E
Real-Fernández
Feliciana
F
Bonache
M Angeles
MA
Le Chevalier-Isaad
Alexandra
A
Chelli
Mario
M
Lubin-Germain
Nadège
N
Uziel
Jacques
J
Rovero
Paolo
P
Lolli
Francesco
F
Papini
Anna Maria
AM
D001324:Autoantigens / Q000737:chemistry* / Q000276:immunology; D006020:Glycopeptides / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood* / Q000276:immunology; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000276:immunology; D011499:Protein Processing, Post-Translational
D001324:Autoantigens; D006020:Glycopeptides; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019158:N-Acetylneuraminic Acid