Antibody Recognition and Conformational Flexibility of a Plaque-Specific β-Amyloid Epitope Modulated by Non-native Peptide Flanking Regions
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- 作者：Marilena Manea ; Adriá ; n Kalá ; szi ; Gá ; bor Mező ; Kata Horvá ; ti ; Andrea Bodor ; Anikó ; Horvá ; th ; Ö ; dö ; n Farkas ; Andrá ; s Perczel ; Michael Przybylski ; Ferenc Hudecz
- 刊名：Journal of Medicinal Chemistry
- 出版年：2008
- 出版时间：March 13, 2008
- 年：2008
- 卷：51
- 期：5
- 页码：1150 - 1161
- 全文大小：1275K
- 年卷期：v.51,no.5(March 13, 2008)
- ISSN：1520-4804
文摘
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.