Antibody Recognition and Conformational Flexibility of a Plaque-Specific beta-Amyloid Epitope Modulated by Non-native Peptide Flanking Regions

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2008
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Kalászi, Adrián
Mezö, Gábor
Horváth, Kata
Bodor, Andrea
Horváth, Anikó
Farkas, Ödön
Perczel, András
Hudecz, Ferenc
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Journal of medicinal chemistry. 2008, 51(5), pp. 1150-1161. ISSN 0022-2623. eISSN 1520-4804. Available under: doi: 10.1021/jm070196e
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Here we report on the synthesis, antibody binding, and QSAR studies of a series of linear and cyclic peptides containing a β-amyloid plaque-specific epitope (Aβ(4 10); FRHDSGY). In these constructs, two or three α-l-Ala, α-d-Ala, or β-Ala residues were introduced at both N- and C-termini of the epitope as non-native flanking sequences. Cyclization of the linear Aβ(4 10) epitope peptide resulted in reduced antibody binding. However, the antibody binding could be fully compensated by insertion of alanine flanks into the corresponding cyclic peptides. These results indicate that the modification of a β-amyloid plaque-specific epitope by combination of cyclization and flanking sequences could generate highly antigenic peptides compared to the native sequence. A novel 3D QSAR method, which explicitly handles conformational flexibility, was developed for the case of such molecular libraries. This method led to the prediction of the binding conformation for the common FRHDSGY sequence.

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ISO 690MANEA, Marilena, Adrián KALÁSZI, Gábor MEZÖ, Kata HORVÁTH, Andrea BODOR, Anikó HORVÁTH, Ödön FARKAS, András PERCZEL, Michael PRZYBYLSKI, Ferenc HUDECZ, 2008. Antibody Recognition and Conformational Flexibility of a Plaque-Specific beta-Amyloid Epitope Modulated by Non-native Peptide Flanking Regions. In: Journal of medicinal chemistry. 2008, 51(5), pp. 1150-1161. ISSN 0022-2623. eISSN 1520-4804. Available under: doi: 10.1021/jm070196e
BibTex
@article{Manea2008Antib-9761,
  year={2008},
  doi={10.1021/jm070196e},
  title={Antibody Recognition and Conformational Flexibility of a Plaque-Specific beta-Amyloid Epitope Modulated by Non-native Peptide Flanking Regions},
  number={5},
  volume={51},
  issn={0022-2623},
  journal={Journal of medicinal chemistry},
  pages={1150--1161},
  author={Manea, Marilena and Kalászi, Adrián and Mezö, Gábor and Horváth, Kata and Bodor, Andrea and Horváth, Anikó and Farkas, Ödön and Perczel, András and Przybylski, Michael and Hudecz, Ferenc}
}
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