Characterization of Asparagine Deamidation in Immunodominant Myelin Oligodendrocyte Glycoprotein Peptide Potential Immunotherapy for the Treatment of Multiple Sclerosis

Mannan (polysaccharide) conjugated with a myelin oligodendrocyte glycoprotein (MOG) peptide, namely (KG)(5)MOG(35–55), represents a potent and promising new approach for the immunotherapy of Multiple Sclerosis (MS). The MOG(35–55) epitope conjugated with the oxidized form of mannan (poly-mannose) via a (KG)(5) linker was found to inhibit the symptoms of MOG(35–55)-induced experimental autoimmune encephalomyelitis (EAE) in mice using prophylactic and therapeutic vaccinated protocols. Deamidation is a common modification in peptide and protein sequences, especially for Gln and Asn residues. In this study, the structural solution motif of deaminated peptides and their functional effects in an animal model for MS were explored. Several peptides based on the MOG(35–55) epitope have been synthesized in which the Asn(53) was replaced with Ala, Asp, or isoAsp. Our results demonstrate that the synthesized MOG peptides were formed to the deaminated products in basic conditions, and the Asn(53) was mainly modified to Asp. Moreover, both peptides (wild type and deaminated derivative) conjugated with mannan (from Saccharomyces cerevisiae) independently inhibited the development of neurological symptoms and inflammatory demyelinating spinal cord lesions in MOG(35–55)-induced EAE. To conclude, mannan conjugated with a deamidated product did not affect the efficacy of the parent peptide.