title: Synthesis and antigenic properties of reduced peptide bond analogues of an immunodominant epitope of the melanoma MART-1 protein.
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 (CH2-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.
authors: Institut de Biologie Moléculaire et Cellulaire, UPR 9021-CNRS, Strasbourg, France.
authors: A
authors: A
authors: Quesnel
authors: A
authors: A
authors: Zerbib
authors: F
authors: F
authors: Connan
authors: J G
authors: JG
authors: Guillet
authors: J P
authors: JP
authors: Briand
authors: J
authors: J
authors: Choppin
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D005449:Fluorenes / Q000737:chemistry; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000276:immunology; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000939:Epitopes; D005449:Fluorenes; D015789:HLA-A2 Antigen; C105787:MART-1-Melan-A(27-35) epitope; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009363:Neoplasm Proteins; D010455:Peptides