Design and Synthesis of a Cyclic Double Mutant Peptide (cyclo(87−99)[A⁹¹,A⁹⁶]MBP₈₇₋₉₉) Induces Altered Responses in Mice after Conjugation to Mannan: Implications in the Immunotherapy of Multiple Sclerosis

Abstract

Altered peptide ligands that alter immune responses are a promising approach to the immunotherapy of multiple sclerosis. Cyclic peptides are of interest because the limited stability of linear peptides restricts their use in vivo. We designed and synthesized a cyclic double mutant peptide from MBP(87-99)-[cyclo(87-99)[A(91),A(96)]MBP(87-99)]. Immunization of mice, in CFA reduced Th1 responses. However, when conjugated to reduced mannan, a significant further reduction of Th1 responses and moderate Th2 responses were induced.