Divergent and convergent synthesis of polymannosylated dibranched antigenic peptide of the immunodominant epitope MBP(83-99)

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• 作者：Irene Friligou ; Fabio Rizzolo ; Francesca Nuti ; Theodore Tselios ; Maria Evangelidou ; Mary Emmanouil ; Maria Karamita ; John Matsoukas ; Mario Chelli ; Paolo Rovero ; Anna Maria Papini
• 关键词：Di-branched antigenic peptide ; Experimental autoimmune encephalomyelitis ; Divergent synthesis ; Convergent synthesis ; Microwave-assisted synthesis ; Mannosylation
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 November, 2013
• 年：2013
• 卷：21
• 期：21
• 页码：6718-6725
• 全文大小：598 K

文摘

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.