Antibody recognition and conformational flexibility of a plaque-specific beta-amyloid epitope modulated by non-native peptide flanking regions.

Abstract

Here we report on the synthesis, antibody binding, and QSAR studies of a series of linear and cyclic peptides containing a beta-amyloid plaque-specific epitope (Abeta(4-10); FRHDSGY). In these constructs, two or three alpha- l-Ala, alpha- d-Ala, or beta-Ala residues were introduced at both N- and C-termini of the epitope as non-native flanking sequences. Cyclization of the linear Abeta(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 beta-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.

• Authors: Marilena Manea, Adrián Kalászi, Gábor Mezo, Kata Horváti, Andrea Bodor, Anikó Horváth, Odön Farkas, András Perczel, Michael Przybylski, Ferenc Hudecz
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 5 Pg. 1150-61 (Mar 13 2008) ISSN: 0022-2623 [Print] United States
• PMID: 18284185 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Antibodies, Monoclonal
• Epitopes
• Peptides, Cyclic
• Solutions
• Alanine

Topics

• Alanine (chemistry)
• Amyloid beta-Peptides (chemistry, immunology)
• Antibodies, Monoclonal (chemistry)
• Enzyme-Linked Immunosorbent Assay
• Epitopes
• Magnetic Resonance Spectroscopy
• Models, Molecular
• Peptides, Cyclic (chemical synthesis, chemistry)
• Plaque, Amyloid (chemistry)
• Protein Binding
• Protein Conformation
• Quantitative Structure-Activity Relationship
• Solutions