CONFGRMATIONALLY DRIVEN RATIONAL DESIGN OF GLYCOPEPTIDES AS SYNTHETIC PROBES FOR THE DETECTION OF AUTOANTIBODIES, BIOMARKERS OF MULTIPLE SCLEROSIS

摘要

The glycopeptide CSF114(Glc) is the first synthetic Multiple Sclerosis Antigenic Probe (MSAP) able to detect with a high-sensitivity specific biomarkers correlating with an antibody-mediated disease form of Multiple Sclerosis (MS). The presence of anti-CSF114(Glc) antibodies is in agreement with the hypothesis of an aberrant glucosylation of native myelin antigen(s) triggering an antibody-mediated MS, in which MSAP is possibly a mimetic of glucosylated native antigen(s) recognized by autoantibodies. Therefore, to unravel the pathogenetic mechanism triggering autoantibodies in MS, we are focusing our efforts on native antigen(s) identification, targets of anti-CSF114(Glc) autoantibodies involved in inflammation and demyelination process. We have previously shown that key elements for autoantibody recognition by MSAP are the β-D-glucopyranosyl moiety linked to an Asn residue by an N-glycosylic bond, and the β-hairpin motif between residues 2 and 14.