Design, synthesis and evaluation of β-lactam antigenic peptide hybrids; unusual opening of the β-lactam ring in acidic media.

beta-Lactam peptides were envisioned as conformational constraints in antigenic peptides (APs). Three different beta-lactam tripeptides of varying flexibility were prepared in solution and incorporated in place of the central part of the altered melanoma associated antigenic peptide Leu(27)-Melan-A(26-35) using solid phase synthesis techniques. Upon TFA cleavage from the solid support, an unexpected opening of the beta-lactam ring occurred with conservation of the amide bond. After adaptation of the solid phase synthesis strategy, beta-lactam peptides were successfully obtained and both opened and closed forms were evaluated for their capacity to bind to the antigen-presenting class-I MHC HLA-A2 protein system. None of the closed beta-lactam peptides bound to HLA-A2, but their opened variants were shown to be moderate to good HLA-A2 ligands, one of them being even capable of stimulating a Melan-A-specific T cell line.