Cytotoxic T lymphocyte epitope analogues containing cis- or trans-4-aminocyclohexanecarboxylic acid residues

In order to improve the immunotherapeutical potential of H-Cys-Leu-Gly-Gly-Leu-Leu-Thr-Met-Val-OH (CLG) peptide, an Epstein-Barr virus (EBV) subdominant epitope derived from the membrane protein LMP2, we have synthesized and tested CLG analogues containing cis- and/or trans-4-aminocyclohexanecarboxylic acid (ACCA) replacing Gly-Gly and/or Thr-Met dipeptide units. All pseudopeptides were tested for metabolic stability and for their capacity to bind HLA-A2 molecules and to sensitize target cells to lysis. All new compounds exhibited higher enzymatic resistance compared to the original CLG and some trans-ACCA-derivatives were able to associate HLA-A2 and to efficiently stimulate CTL responses directed against the CLG natural epitope.