Conformation-activity relationship of designed glycopeptides as synthetic probes for the detection of autoantibodies, biomarkers of multiple sclerosis.
Sera from patients suffering from autoimmune disorders often contain multiple types of autoantibodies, some of which can be exclusive of a disease and thus used as biomarkers for diagnosis. Identification of these autoantibodies, as disease biomarkers, should be achieved using native antigens in simple biological assays. However, posttranslational modifications, such as glycosylation, may play a fundamental role for specific autoantibody recognition. In line with these observations, we described synthetic glycopeptides able to detect high autoantibody titers in sera of patients affected by multiple sclerosis, an inflammatory, demyelinating disease of the central nervous system. We describe here the conformation-activity relationship of a focused library of glycopeptides based on structural diversity, with the aim of defining the structural requirements for the interaction of these glycopeptide antigens with specific autoantibodies. The final goal is the optimization of an antigenic probe for multiple sclerosis, to be used in the development of a simple diagnostic test based on an immunoenzymatic assay. The reported results clearly indicate that glycopeptides able to reveal high antibody titers in multiple sclerosis sera are characterized by a type I' beta-turn around the minimal epitope Asn(Glc), which allows an efficient exposure of this moiety to antibodies interactions, in the context of a solid-phase immunoenzymatic assay.
Carotenuto
Alfonso
A
Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, I-80131 Naples, Italy.
D'Ursi
Anna Maria
AM
Mulinacci
Barbara
B
Paolini
Ilaria
I
Lolli
Francesco
F
Papini
Anna Maria
AM
Novellino
Ettore
E
Rovero
Paolo
P
D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015195:Drug Design; D006020:Glycopeptides / Q000737:chemistry / Q000276:immunology*; D015335:Molecular Probes / Q000737:chemistry / Q000276:immunology*; D009103:Multiple Sclerosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D019151:Peptide Library; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D001323:Autoantibodies; D015415:Biomarkers; D006020:Glycopeptides; D015335:Molecular Probes; D019151:Peptide Library