Peptide analogues of a subdominant epitope expressed in EBV-associated tumors: Synthesis and immunological activity

M. Marastoni, M. Bazzaro, F. Micheletti, R. Gavioli, R. Tomatis

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2370-2373
Number of pages4
JournalJournal of Medicinal Chemistry
Volume44
Issue number14
DOIs
StatePublished - Jul 5 2001

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