TY - JOUR
T1 - Peptide analogues of a subdominant epitope expressed in EBV-associated tumors
T2 - Synthesis and immunological activity
AU - Marastoni, M.
AU - Bazzaro, M.
AU - Micheletti, F.
AU - Gavioli, R.
AU - Tomatis, R.
PY - 2001/7/5
Y1 - 2001/7/5
N2 - H-Cys-Leu-Gly-Gly-Leu-Leu-Thr-Met-Val-OH (CLG) peptide is an EBV subdominant epitope that represents the target of HLA-A2 restricted CTL responses. The CLG peptide has low affinity for HLA-A2 and does not produce stable complexes, both factors that determine weal CTL responses. In contrast, the [Tyr1, Ala3]CLG (YLA) analogue showed high affinity for HLA A2 molecules and efficiently stimulated CLG-specific CTL precursors. Nevertheless, this modified epitope showed low enzymatic stability. To further improve the immunotherapeutical potential of this "improved epitope", we have synthesized and tested YLA analogues containing different modifications next to the scissile peptide bond. Among the analogues we found three peptides, with higher enzymatic resistance, that efficiently stimulate CTL responses. These peptides may be used for EBV-specific immunotherapies.
AB - H-Cys-Leu-Gly-Gly-Leu-Leu-Thr-Met-Val-OH (CLG) peptide is an EBV subdominant epitope that represents the target of HLA-A2 restricted CTL responses. The CLG peptide has low affinity for HLA-A2 and does not produce stable complexes, both factors that determine weal CTL responses. In contrast, the [Tyr1, Ala3]CLG (YLA) analogue showed high affinity for HLA A2 molecules and efficiently stimulated CLG-specific CTL precursors. Nevertheless, this modified epitope showed low enzymatic stability. To further improve the immunotherapeutical potential of this "improved epitope", we have synthesized and tested YLA analogues containing different modifications next to the scissile peptide bond. Among the analogues we found three peptides, with higher enzymatic resistance, that efficiently stimulate CTL responses. These peptides may be used for EBV-specific immunotherapies.
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U2 - 10.1021/jm001136a
DO - 10.1021/jm001136a
M3 - Article
C2 - 11428932
AN - SCOPUS:0035811456
SN - 0022-2623
VL - 44
SP - 2370
EP - 2373
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 14
ER -