title: Divergent and convergent synthesis of polymannosylated dibranched antigenic peptide of the immunodominant epitope MBP(83-99).
abstract: Multiple antigenic peptide (MAP) systems are dendrimeric structures bearing multiple copies of identical or different peptide epitopes, and they have been demonstrated to show enhanced immunogenicity. Herein, we report the direct (divergent) and indirect (convergent) synthesis, using contemporary synthetic approaches, of a di-branched antigenic peptide (di-BAP) containing the immunodominant epitope MBP(83-99), which is implicated in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). The direct synthesis (di-BAP 1) was performed using microwave irradiation. The indirect synthesis (di-BAP 2) was carried out performing an efficient chemoselective coupling reaction through the formation of a thioether bond. Both di-BAPs were conjugated to polysaccharide mannan since mannosylation is a promising technique to achieve modulation in immune response. The conjugation was achieved through free amino groups of both di-BAPs via the formation of Schiff bases. The mannan-conjugated di-BAPs were further evaluated in vivo in a prophylactic vaccination protocol, prior to EAE induction in Lewis rats.
authors.affiliation: Department of Chemistry, University of Patras, GR-26504 Patras, Greece; Laboratory of Peptide & Protein Chemistry & Biology, Italy; Laboratory of Peptide & Protein Chemistry & Biology, France; c/o Department of Chemistry "Ugo Schiff", University of Florence, I-50019 Sesto Fiorentino, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Friligou
authors.forename: Fabio
authors.initials: F
authors.lastname: Rizzolo
authors.forename: Francesca
authors.initials: F
authors.lastname: Nuti
authors.forename: Theodore
authors.initials: T
authors.lastname: Tselios
authors.forename: Maria
authors.initials: M
authors.lastname: Evangelidou
authors.forename: Mary
authors.initials: M
authors.lastname: Emmanouil
authors.forename: Maria
authors.initials: M
authors.lastname: Karamita
authors.forename: John
authors.initials: J
authors.lastname: Matsoukas
authors.forename: Mario
authors.initials: M
authors.lastname: Chelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Rovero
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Papini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D008351:Mannans / Q000737:chemistry*; D008872:Microwaves; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D011107:Polylysine / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D012545:Schiff Bases / Q000737:chemistry
chemical_list: D000939:Epitopes; D008351:Mannans; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010455:Peptides; D012545:Schiff Bases; D011107:Polylysine; C097323:polymannose
keywords: Convergent synthesis; Di-branched antigenic peptide; Divergent synthesis; Experimental autoimmune encephalomyelitis; Mannosylation; Microwave-assisted synthesis