Projects / Autoimmune mediate diseases / Multiple Sclerosis

SPPS of glucosylated multiple antigen peptides (MAPs) as synthetic probes for detection of autoantibodies in multiple sclerosis patients’ sera

Profiles

Multiple Sclerosis (MS) is the most known chronic, inflammatory, demyelinating disease of the central nervous system (CNS), characterized by a progressive neurodegeneration, caused by an autoimmune response to self-antigens in genetically susceptible individuals. It is nowadays known that post-translational modifications may affect the immunogenicity of self-protein antigens, triggering an autoimmune response and creating neo-antigens; in particular aberrant glycosylations affect various parts of the immune response and have profound effects on immune tolerance. In previous studies we demonstrated the value of the glycopeptide CSF114(Glc) which, by virtue of the particular type I’ β-turn structure, optimally exposes the minimal epitope Asn(Glc) to autoantibody recognizing in ELISA in multiple sclerosis patients’ sera. ELISA assays allowed to conclude that the ability in detecting autoantibodies in multiple sclerosis sera was stricktly linked to saccharidic moieties and to conformation around minimal epitope of the antigenic glycopeptide.Herein, taking advantage of such considerations, we focused our attention on the synthesis of a little library of lysine branched multiple antigen peptides (MAPs), containing the minimal epitope Asn(Glc), in an attempt to increase the antigenicity of linear peptide sequences.With this aim, we performed the SPPS of glucosylated MAPs via the building block approach, studying the role of different long spacers on the dendrimeric core, and the role of different peptide sequences around the sugar moiety, in order to optimize the synthetic process and to evaluate the influence on the affinity and specificity in SP-ELISA.

SP-ELISA performed on 16 MS patients and compared to 13 blood donors (BD) allowed to select ct35 as multivalent ligand for SP-ELISA