Partially Modified Retro-Inverso Pseudopeptides as Non-natural Ligands for the Human Class I Histocompatibility Molecule HLA-A2
| العنوان: | Partially Modified Retro-Inverso Pseudopeptides as Non-natural Ligands for the Human Class I Histocompatibility Molecule HLA-A2 |
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| المؤلفون: | Jean-Paul Briand, Jean-Gérard Guillet, Jeannine Choppin, Gilles Guichard, Sylviane Muller, Marina Ostankovitch, Roland Graff, Francine Connan |
| المصدر: | Journal of Medicinal Chemistry. 39:2030-2039 |
| بيانات النشر: | American Chemical Society (ACS), 1996. |
| سنة النشر: | 1996 |
| مصطلحات موضوعية: | chemistry.chemical_classification, Viral matrix protein, Stereochemistry, Chemistry, Ligand, Molecular Sequence Data, Peptide binding, Peptide, Spectrometry, Mass, Fast Atom Bombardment, Ligands, Orthomyxoviridae, Chemical synthesis, Histocompatibility, Viral Matrix Proteins, chemistry.chemical_compound, Residue (chemistry), Malonate, HLA-A2 Antigen, Drug Discovery, Tumor Cells, Cultured, Humans, Molecular Medicine, Amino Acid Sequence, Peptides, Protein Binding |
| الوصف: | Syntheses of a series of partially modified retro-inverso analogues of the antigenic peptide M58-66 derived from the influenza virus matrix protein are reported. The retro-inverso modification phi(NH-CO) was obtained by replacement of two successive amino acid residues with a 2-substituted malonate derivative and gem-diaminoalkyl residue. The resulting compounds 1-8 were tested for their binding to the human histocompatibility class I molecule HLA-A2 in an assembly assay using lysates of peptide transporter-deficient cells T2. Specific peptide-dependent HLA-A2 assembly was revealed by an enzyme-linked immunosorbent assay. Significant HLA-A2 assembly was detected in the presence of analogues [gGly58-(S)mLeu59]-M58-66 (1a), [gGly61-(R,S)mPhe62]M58-66 (4), [gVal63-(R,S)mPhe64]M58-66 (6), and [gPhe64-(R,S)mAla65]M58-66 (7). The introduction of the retro-inverso modification between P2-P3, P3-P4, P5-P6, and P8-P9 (compounds 2, 3, 5, and 8, respectively) however led to a dramatic reduction in peptide binding to HLA-A2. Interestingly, compound 1a which contains modification between P1-P2 was found to be the most potent analogue, being able to retain the original HLA-A2 binding profile of the parent peptide M58-66. Taken together, these results and recent binding data obtained in the context of murine MHC class I molecule H-2Kd suggest that the incorporation of peptide bond surrogates in MHC class I-restricted epitopes is a useful approach to design molecules having both increased stability and high MHC-binding capacity. Depending on their agonist or antagonist effects at the T-cell receptor, such non-natural MHC ligands are likely to find many applications in the development of peptide-based vaccines or as potential therapeutic agents in the treatment of allergies and autoimmune diseases. |
| تدمد: | 1520-4804 0022-2623 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::440d16e36ad966a7727f440acc744c5eTest https://doi.org/10.1021/jm9509511Test |
| رقم الانضمام: | edsair.doi.dedup.....440d16e36ad966a7727f440acc744c5e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
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