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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1996-7-18
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
39
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2030-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8642561-Amino Acid Sequence,
pubmed-meshheading:8642561-HLA-A2 Antigen,
pubmed-meshheading:8642561-Humans,
pubmed-meshheading:8642561-Ligands,
pubmed-meshheading:8642561-Molecular Sequence Data,
pubmed-meshheading:8642561-Orthomyxoviridae,
pubmed-meshheading:8642561-Peptides,
pubmed-meshheading:8642561-Protein Binding,
pubmed-meshheading:8642561-Spectrometry, Mass, Fast Atom Bombardment,
pubmed-meshheading:8642561-Tumor Cells, Cultured,
pubmed-meshheading:8642561-Viral Matrix Proteins
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pubmed:year |
1996
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pubmed:articleTitle |
Partially modified retro-inverso pseudopeptides as non-natural ligands for the human class I histocompatibility molecule HLA-A2.
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pubmed:affiliation |
Institut de Biologie Moléculaire et Cellulaire, UPR 9021 CNRS, Strasbourg, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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