Design, structural, and immuno-analytical properties of antigenic bioconjugates comprising a beta-amyloid-plaque specific epitope

Biopolymers
Marilena ManeaGábor Mezo

Abstract

Immunotherapeutic approaches are investigated for treatment of neurodegenerative diseases of the Alzheimer's dementia (AD) type. The identification of a beta-amyloid-plaque specific epitope, Abeta(4-10) (4FRHDSGY10), recognized by therapeutically active antibodies from transgenic AD mice could provide the basis for the development of AD vaccines. Here we report on the synthesis, structural and immuno-analytical characterization of bioconjugates comprising the beta-amyloid(4-10) epitope as new vaccine lead structures against Alzheimer's disease. To produce antigenic bioconjugates, potential immunogens, the epitope peptide elongated by a cysteine residue or a cysteinyl-pentaglycine hexapeptide unit either at the N- or C-terminus was attached via a thioether bond to synthetic oligopeptide carriers, such as oligotuftsin derivatives, sequential oligopeptide carrier, or lysine dendrimer. The antigenic properties of these constructs were determined by enzyme-linked immunosorbent assay (ELISA) using an anti-Abeta(1-17) monoclonal antibody. Our results indicate that the major factors which influence the antibody binding of the Abeta(4-10) epitope are (i) the epitope topology and (ii) the presence of a spacer moiety between the carrier a...Continue Reading

References

Aug 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·David S GelinasJoanne McLaurin
Jan 7, 2005·Journal of Peptide Science : an Official Publication of the European Peptide Society·Gábor MezöFerenc Hudecz
Oct 26, 2005·Journal of Peptide Science : an Official Publication of the European Peptide Society·Gábor MezöFerenc Hudecz

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Citations

Mar 26, 2009·Journal of Peptide Science : an Official Publication of the European Peptide Society·Kata HorvátiSzilvia Bosze
Jan 13, 2018·Journal of Peptide Science : an Official Publication of the European Peptide Society·Raluca ȘtefănescuMichael Przybylski
Oct 31, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martin CornilletLeonor Nogueira
Jan 27, 2019·International Journal of Molecular Sciences·Vo Van Giau, Seong Soo A An

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