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

Autor: Maria-Eleni Androutsou, Theodore Tselios, Simona Golic Grdadolnik, Lesley Probert, Areti Gkika, Agathi Nteli, Anastasia Dagkonaki, Maria Avloniti
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
asparagine deamidation
experimental autoimmune encephalomyelitis
Peptide
multiple sclerosis
Epitope
Mannans
lcsh:Chemistry
Mice
0302 clinical medicine
immune system diseases
Asparagine
Deamidation
lcsh:QH301-705.5
Spectroscopy
Mannan
chemistry.chemical_classification
biology
Experimental autoimmune encephalomyelitis
hemic and immune systems
General Medicine
Computer Science Applications
Biochemistry
Deamination
030220 oncology & carcinogenesis
myelin oligodentrocyte glycoprotein
Female
Immunotherapy
Encephalomyelitis
Autoimmune
Experimental
Catalysis
Article
Myelin oligodendrocyte glycoprotein
Inorganic Chemistry
03 medical and health sciences
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
Organic Chemistry
Wild type
medicine.disease
Peptide Fragments
Rats
nervous system diseases
carbohydrates (lipids)
Mice
Inbred C57BL
nuclear magnetic resonance
030104 developmental biology
chemistry
nervous system
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Myelin-Oligodendrocyte Glycoprotein
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 7566, p 7566 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 20
ISSN: 1661-6596
1422-0067
Popis: Mannan (polysaccharide) conjugated with a myelin oligodendrocyte glycoprotein (MOG) peptide, namely (KG)5MOG35&ndash
55, represents a potent and promising new approach for the immunotherapy of Multiple Sclerosis (MS). The MOG35&ndash
55 epitope conjugated with the oxidized form of mannan (poly-mannose) via a (KG)5 linker was found to inhibit the symptoms of MOG35&ndash
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 MOG35&ndash
55 epitope have been synthesized in which the Asn53 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 Asn53 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 MOG35&ndash
55-induced EAE. To conclude, mannan conjugated with a deamidated product did not affect the efficacy of the parent peptide.
Databáze: OpenAIRE
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