Glucosylated peptides in autoimmune diseases: synthetic strategies and application to antibody detection and capture

The main purpose of this thesis was to develop peptide probes to detect and isolate specific and high affinity antibodies from sera of patients suffering from multiple sclerosis (MS). We selected a di-glucosylated adhesin HMW1 peptide as the shortest sequence up to now able to compete with the highest affinity with anti-N(Glc) IgM binding. 40 kDa dextran was modified with propargyl groups and used as a scaffold to conjugate by CuAAC the di-glucosylated peptide. This novel polymeric structure was proven to dramatically increase binding potency of IgGs and IgMs in MS sera. Abs from a representative MS serum, were successfully purified on a sepharose resin specifically modified with the adhesin peptide-dextran conjugate, as confirmed by ELISA. This result appears promising as a proof-of-concept of the selective removal of circulating autoantibodies (possibly perpetuating nonself recognition) that could likely lead to develop a specific apheresis-based device.