Melan-A (26-35) peptide

Native Melan-A (26-35) decapeptide derives from the melanocyte lineage-specific protein Melan-A/MART-1, which is expressed in almost 75-100% of primary and metastatic melanomas. The region 26-35 of Melan-A protein acts as an antigenic peptide that is recognized by CD8+ tumor-reactive cytolytic T lymphocytes (CTLs) for designing antigen-specific cancer vaccines1. It has been shown that CD8+ Melan-A-specific CTLs isolated from melanoma patients efficiently lyse the Melan-A-expressing HLA-A*0201+ melanoma cell line. However, CTLs preferentially recognize the Melan-A (26-35) peptide as compared with the Melan-A (27-35) peptide. Moreover, the Melan-A (26-35) A27L analog (ELAGIGILTV) has a higher binding affinity to HLA-A*0201 than the native Melan-A (26-35) peptide (EAAGIGILTV), and consequently displays more potent antigenicity and immunogenicity. It has been reported that the concentration of Melan-A (26-35) A27L analog required to obtain 50% of maximal antigenic activity (EC50) is 0.01nM, whereas that of the native Melan-A (26-35) peptide is 0.25nM1. Therefore, the relative activity of Melan-A (26-35) A27L analog is 25 fold higher than that of the native Melan-A (26-35) peptide. Furthermore, functional competition assay has shown that the concentration of Melan-A (26-35) A27L analog required to achieve 50% inhibition (IC50) of tumor lysis is 2nM, which is 10 fold lower than that of the native Melan-A (26-35) peptide. Regarding peptide stability in human serum, the half-lifes (t1/2) of the native Melan-A (26-35) peptide and the A27L analog are quite similar (45 and 40min, respectively) as measured by HPLC-ESI-MS, but much higher than that of the Melan-A (27-35) nonapeptide (5min) .