title: Synthetic dimeric Aβ(28-40) mimics the complex epitope of human anti-Aβ autoantibodies against toxic Aβ oligomers.
abstract: Covalently linked carboxyl-terminal segments of the β-amyloid peptide (Aβ) were tested for their qualification as minimal conformational epitopes of the naturally occurring human autoantibodies against β-amyloid (nAbs-Aβ). nAbs-Aβ specifically recognize the toxic oligomers of Aβ and not the monomeric or the fibrillar forms of Aβ. The synthetic dimers of Aβ(28-40) described herein mimic the toxic Aβ oligomers but are not kinetic intermediates with uncertain compositions. CD spectra identified a surprisingly rich conformational behavior of selected miniamyloids. We observed a highly cooperative conformational transition of β-sheet to α-helix upon the addition of the helix enforcing co-solvent hexafluoroisopropanol. The CD curves of dimer 9 resembled, in a completely reversible manner, the CD spectra measured during the irreversible fibrillation of the parent Aβ(1-40). Synthetic peptide epitopes with high affinities for nAbs-Aβ are needed to identify the physiological roles of nAbs-Aβ and are promising epitopes for vaccination experiments.
authors.affiliation: Faculty of Chemistry, Philipps University of Marburg, Hans-Meerwein-Strasse, D-35032 Marburg.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Roeder
authors.affiliation: Department of Neurology, Philipps University of Marburg, Baldingerstrasse, D-35043 Marburg, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Roettger
authors.affiliation: Department of Neurology, Philipps University of Marburg, Baldingerstrasse, D-35043 Marburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Stündel
authors.affiliation: Department of Neurology, Philipps University of Marburg, Baldingerstrasse, D-35043 Marburg, Germany. Electronic address: dodel@med.uni-marburg.de.
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
authors.affiliation: Faculty of Chemistry, Philipps University of Marburg, Hans-Meerwein-Strasse, D-35032 Marburg. Electronic address: geyer@staff.uni-marburg.de.
authors.forename: Armin
authors.initials: A
authors.lastname: Geyer
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured; D002942:Circular Dichroism; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D051379:Mice; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D000939:Epitopes
keywords: Alzheimer Disease; Amyloid; Autoantibodies; Neuroimmunology; Neurological Diseases; Peptide Chemical Synthesis; Peptide Conformation; Protein Aggregation