Designed glycopeptides with different beta-turn types as synthetic probes for the detection of autoantibodies as biomarkers of multiple sclerosis.
Circulating autoantibodies have been recognized as disease biomarkers of autoimmune diseases. We have previously disclosed a synthetic glycopeptide that is able to detect specific autoantibodies in sera of patients who are affected by multiple sclerosis (MS). This glycopeptide is characterized by a type I' beta-turn around the minimal epitope Asn(Glc) that allows an efficient exposure of this moiety to antibody interactions in the context of a solid-phase immunoenzymatic assay. With the aim of optimizing the glycopeptide-antibody interactions, we analyze a series of new glycopeptides based on different turn structures. Our results confirm the role of conformation in the recognition and binding of synthetic antigenic probes to MS autoantibodies. Glycopeptide 2, which is characterized by a type I beta-turn around the minimal epitope Asn(Glc), shows the highest antibody affinity (IC50 = 11.8 nM), and thus it appears to be a promising tool for the detection of specific autoantibodies as MS biomarker in patients' sera.
Carotenuto
Alfonso
A
Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, via D. Montesano 49, I-80131 Naples, Italy.
Alcaro
Maria Claudia
MC
Saviello
Maria Rosaria
MR
Peroni
Elisa
E
Nuti
Francesca
F
Papini
Anna Maria
AM
Novellino
Ettore
E
Rovero
Paolo
P
D000915:Antibody Affinity; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015195:Drug Design; D006020:Glycopeptides / Q000138:chemical synthesis / Q000276:immunology; D006801:Humans; D015335:Molecular Probes / Q000138:chemical synthesis*; D009103:Multiple Sclerosis / Q000175:diagnosis*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D001323:Autoantibodies; D015415:Biomarkers; D006020:Glycopeptides; D015335:Molecular Probes