| |
[摘要]：The use of antagonist peptides derived from the myelin sheath constitutes a promising therapeutic approach for multiple sclerosis (MS). Cyclization of peptide analogs is of great interest, since the limited stability of linear peptides restricts their potential as therapeutic agents. Herein, the authors designed and synthesized a no. of cyclic peptides by mutating TCR contact sites of the MBP83-99 epitope. A no. of cyclic analogs were tested for their ability to inhibit (antagonize) Th1 (IFN-g) responses, and cyclo(83-99)[A91]MBP83-99 mutant peptide was the most efficient inhibitor. The authors demonstrated that cyclo(83-99)[A91]MBP83-99 peptide emulsified in CFA enhanced Th2 (IL-4) and antibody responses in vivo. Moreover, immunization of mice with antagonist cyclo(83-99)[A91]MBP83-99 peptide conjugated to reduced mannan enhanced IL-4 responses compared to cyclo(83-99)MBP83-99 peptide. Thus, cyclized peptides, which offer greater stability and enhanced responses, are novel leads for the immunotherapy of many diseases, such as MS. In particular, cyclo(83-99)[A91]MBP83-99 is a promising mutant peptide analog for the potential treatment of MS. |
|
