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Three Structural Features of Functional Food Components and Herbal Medicine with Amyloid β42 Anti-Aggregation Properties
Open AccessArticle

Interference with Amyloid-β Nucleation by Transient Ligand Interaction

1
Institute of Complex Systems, Structural Biochemistry (ICS-6), Forschungszentrum Jülich, 52425 Jülich, Germany
2
Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany
3
Institute of Theoretical and Computational Chemistry, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(11), 2129; https://doi.org/10.3390/molecules24112129
Received: 7 May 2019 / Revised: 2 June 2019 / Accepted: 4 June 2019 / Published: 5 June 2019
(This article belongs to the Special Issue Amyloid Inhibitors and Modulators)
Amyloid-β peptide (Aβ) is an intrinsically disordered protein (IDP) associated with Alzheimer’s disease. The structural flexibility and aggregation propensity of Aβ pose major challenges for elucidating the interaction between Aβ monomers and ligands. All-D-peptides consisting solely of D-enantiomeric amino acid residues are interesting drug candidates that combine high binding specificity with high metabolic stability. Here we characterized the interaction between the 12-residue all-D-peptide D3 and Aβ42 monomers, and how the interaction influences Aβ42 aggregation. We demonstrate for the first time that D3 binds to Aβ42 monomers with submicromolar affinities. These two highly unstructured molecules are able to form complexes with 1:1 and other stoichiometries. Further, D3 at substoichiometric concentrations effectively slows down the β-sheet formation and Aβ42 fibrillation by modulating the nucleation process. The study provides new insights into the molecular mechanism of how D3 affects Aβ assemblies and contributes to our knowledge on the interaction between two IDPs. View Full-Text
Keywords: amyloid-β peptides; aggregation; complex formation; D-enantiomeric peptide; intrinsically disordered protein amyloid-β peptides; aggregation; complex formation; D-enantiomeric peptide; intrinsically disordered protein
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MDPI and ACS Style

Zhang, T.; Loschwitz, J.; Strodel, B.; Nagel-Steger, L.; Willbold, D. Interference with Amyloid-β Nucleation by Transient Ligand Interaction. Molecules 2019, 24, 2129.

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