Synthesis and antigenic properties of reduced peptide bond analogues of animmunodominant epitope of the melanoma MART-1 protein

Backbone modifications have been introduced into the melanoma derived pepti de MART-1((27-35)) to increase its binding to class I major histocompatibil ity complex HLA-A2 molecule, and ultimately to enhance its inununogenicity. Each analogue was obtained by replacing one peptide bond at a time in the natural epitope by the aminomethylene (CH2-NH) surrogate. AU analogues disp layed an increased resistance to proteolysis. Interestingly, the comparativ e results showed that five analogues bound more efficiently to HLA-A2 than the parent peptide. On the other hand, two pseudopeptide/HLA-A2 complexes w ere recognized by one melanoma-specific T cell clone. Close examination of the impact of such modifications at the molecular level provides useful sup ports for the rational design of stable compounds with applications in anti -tumour specific immunotherapy and in vaccine development. Copyright (C) 20 01 European Peptide Society and John Wiley & Sons, Ltd.