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 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.
Bodé
Catherine A
CA
Laboratory for Organic and Biomimetic Chemistry, Department of Organic Chemistry, Ghent University, B-9000 Gent, Belgium.
Bechet
Tom
T
Prodhomme
Emmanuel
E
Gheysen
Katelijne
K
Gregoir
Pieter
P
Martins
José C
JC
Muller
Claude P
CP
Madder
Annemieke
A
D000911:Antibodies, Monoclonal / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D001647:Bile Acids and Salts / Q000737:chemistry*; D000939:Epitopes / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008458:Measles Vaccine; D008459:Measles virus / Q000276:immunology*; D008968:Molecular Conformation; D018716:Molecular Mimicry; D010446:Peptide Fragments / Q000276:immunology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000276:immunology*; D011487:Protein Conformation; D055550:Protein Stability
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D001647:Bile Acids and Salts; D000939:Epitopes; D006389:Hemagglutinins, Viral; D008458:Measles Vaccine; D010446:Peptide Fragments; D010456:Peptides, Cyclic