Towards the conformational mimicry of the measles virus HNE loop: design, synthesis and biological evaluation of a cyclic bile acid-peptide conjugate

The current article reports the design, synthesis and biochemical evaluation of a cyclic bile acid-peptide conjugate as a mimic of the loop-like structure of the measles virus haemagglutinin noose epitope (HNE). This macrocyclic structure was assembled by solid phase synthesis. Scaffold-peptide ring...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2009-01, Vol.7 (17), p.3391-3399
Main Authors: Bodé, Catherine A, Bechet, Tom, Prodhomme, Emmanuel, Gheysen, Katelijne, Gregoir, Pieter, Martins, José C, Muller, Claude P, Madder, Annemieke
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - immunology
Antigens, Viral - immunology
Bile Acids and Salts - chemistry
Epitopes - immunology
Hemagglutinins, Viral - immunology
Humans
Magnetic Resonance Spectroscopy
Measles Vaccine
Measles virus - immunology
Molecular Conformation
Molecular Mimicry
Peptide Fragments - immunology
Peptides, Cyclic - chemical synthesis
Peptides, Cyclic - immunology
Protein Conformation
Protein Stability
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Summary:The current article reports the design, synthesis and biochemical evaluation of a cyclic bile acid-peptide conjugate as a mimic of the loop-like structure of the measles virus haemagglutinin noose epitope (HNE). This macrocyclic structure was assembled by solid phase synthesis. Scaffold-peptide ring closure was achieved via the introduction of a succinate linker. After disulfide bridge formation with iodine, the desired 14 amino acid cyclic conjugate was obtained with overall yields between 15 and 35%. NMR analysis supports the presence of a helical conformation in the Q384-G388 pentapeptide portion, in agreement with the organisation of this chain in the native protein. The compound was found to have increased biostability compared to stabilised linear peptides, displayed good binding towards monoclonal antibodies known to bind to HNE and thus has potential in an alternative peptide-based measles vaccine.
ISSN:1477-0520
1477-0539
DOI:10.1039/b907395g