Synthesis and antigenic properties of reduced peptide bond analogues of an immunodominant epitope of the melanoma MART-1 protein

✍ Scribed by Anne Quesnel; Anne Zerbib; Francine Connan; Jean-Gérard Guillet; Jean-Paul Briand; Jeannine Choppin

• Book ID: 105360125
• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 114 KB
• Volume: 7
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.311

✦ Synopsis

Abstract

Backbone modifications have been introduced into the melanoma derived peptide MART‐1~(27‐35)~ to increase its binding to class I major histocompatibility complex HLA‐A2 molecule, and ultimately to enhance its immunogenicity. Each analogue was obtained by replacing one peptide bond at a time in the natural epitope by the aminomethylene (CH~2~‐NH) surrogate. All analogues displayed an increased resistance to proteolysis. Interestingly, the comparative results showed that five analogues bound more efficiently to HLA‐A2 than the parent peptide. On the other hand, two pseudopeptide/HLA‐A2 complexes were recognized by one melanoma‐specific T cell clone. Close examination of the impact of such modifications at the molecular level provides useful supports for the rational design of stable compounds with applications in anti‐tumour specific immunotherapy and in vaccine development. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.