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

Marion Tarbe, Itxaso Azcune, Eva Balentová, John J. Miles, Emily E. Edwards, Kim M. Miles, Priscilla Do, Brian M. Baker, Andrew K. Sewell, Jesus M. Aizpurua, Céline Douat-Casassus, Stéphane Quideau

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

β-Lactam peptides were envisioned as conformational constraints in antigenic peptides (APs). Three different β-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-A26-35 using solid phase synthesis techniques. Upon TFA cleavage from the solid support, an unexpected opening of the β-lactam ring occurred with conservation of the amide bond. After adaptation of the solid phase synthesis strategy, β-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 β-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.

Original languageEnglish
Pages (from-to)5345-5353
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume8
Issue number23
DOIs
Publication statusPublished - 7 Dec 2010
Externally publishedYes

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