Your browser doesn't support javascript.
loading
Synthesis and Biological Evaluation of Hapten-Clicked Analogues of The Antigenic Peptide Melan-A/MART-126(27L)-35.
Tarbe, Marion; Miles, John J; Edwards, Emily S J; Miles, Kim M; Sewell, Andrew K; Baker, Brian M; Quideau, Stéphane.
Afiliação
  • Tarbe M; Université de Bordeaux, ISM (CNRS-UMR 5255), 351 cours de la Libération, 33405, Talence Cedex, France.
  • Miles JJ; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
  • Edwards ESJ; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
  • Miles KM; Department of Immunology and Pathology, Central Clinical School, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria, 3004, Australia.
  • Sewell AK; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
  • Baker BM; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
  • Quideau S; Department of Chemistry & Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556, USA.
ChemMedChem ; 15(9): 799-807, 2020 05 06.
Article em En | MEDLINE | ID: mdl-32162475
A click-chemistry-based approach was implemented to prepare peptidomimetics designed in silico and made from aromatic azides and a propargylated GIGI-mimicking platform derived from the altered Melan-A/MART-126(27L)-35 antigenic peptide ELAGIGILTV. The CuI -catalyzed Huisgen cycloaddition was carried out on solid support to generate rapidly a first series of peptidomimetics, which were evaluated for their capacity to dock at the interface between the major histocompatibility complex class-I (MHC-I) human leucocyte antigen (HLA)-A2 and T-cell receptors (TCRs). Despite being a weak HLA-A2 ligand, one of these 11 first synthetic compounds bearing a p-nitrobenzyl-triazole side chain was recognized by the receptor proteins of Melan-A/MART-1-specific T-cells. After modification of the N and C termini of this agonist, which was intended to enhance HLA-A2 binding, one of the resulting seven additional compounds triggered significant T-cell responses. Thus, these results highlight the capacity of naturally circulating human TCRs that are specific for the native Melan-A/MART-126-35 peptide to cross-react with peptidomimetics bearing organic motifs structurally different from the native central amino acids.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligopeptídeos / Antígeno MART-1 / Haptenos Limite: Humans Idioma: En Revista: ChemMedChem Assunto da revista: FARMACOLOGIA / QUIMICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: França País de publicação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligopeptídeos / Antígeno MART-1 / Haptenos Limite: Humans Idioma: En Revista: ChemMedChem Assunto da revista: FARMACOLOGIA / QUIMICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: França País de publicação: Alemanha