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.
Dipartimento di Scienze Farmaceutiche e Centro di Biotecnologie, Via Fossato di Mortara 17-19, Università di Ferrara, I-44100 Ferrara, Italy. mrn@dns.unife.it
Mauro
M
Marastoni
Martina
M
Bazzaro
Fabiola
F
Micheletti
Riccardo
R
Gavioli
Roberto
R
Tomatis
D000598:Amino Acids, Cyclic / Q000737:chemistry / Q000276:immunology* / Q000493:pharmacokinetics; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry / Q000276:immunology* / Q000493:pharmacokinetics; D003601:Cytotoxicity Tests, Immunologic; D004355:Drug Stability; D000939:Epitopes / Q000737:chemistry*; D015789:HLA-A2 Antigen / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000276:immunology
D000598:Amino Acids, Cyclic; D003509:Cyclohexanecarboxylic Acids; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D000939:Epitopes; D015789:HLA-A2 Antigen; D009842:Oligopeptides; D014763:Viral Matrix Proteins; C010124:4-aminocyclohexanecarboxylic acid