Hydrophobic Modification of Carboxyl-Terminated Polyamidoamine Dendrimer Surface Creates a Potent Inhibitor of Amyloid-β Fibrillation
Amyloid β-peptide (Aβ) fibrillogenesis is a major hallmark of Alzheimer's disease (AD); inhibition of Aβ fibrillation is thus considered as a promising strategy for AD prevention and treatment. Our group has previously proposed the hydrophobic binding-electrostatic repulsion (HyBER) hypothesis,...
| Veröffentlicht in: | Langmuir : the ACS journal of surfaces and colloids. - 1992. - 34(2018), 47 vom: 27. Nov., Seite 14419-14427 |
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| Weitere Verfasser: | , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2018
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| Zugriff auf das übergeordnete Werk: | Langmuir : the ACS journal of surfaces and colloids |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Amyloid beta-Peptides Dendrimers PAMAM Starburst Peptide Fragments Protein Aggregates amyloid beta-protein (1-42) |
| Zusammenfassung: | Amyloid β-peptide (Aβ) fibrillogenesis is a major hallmark of Alzheimer's disease (AD); inhibition of Aβ fibrillation is thus considered as a promising strategy for AD prevention and treatment. Our group has previously proposed the hydrophobic binding-electrostatic repulsion (HyBER) hypothesis, which provides guidance for the design of new amyloid inhibitors. Inspired by the HyBER hypothesis, we have herein proposed to synthesize hydrophobic-modified generation 5 carboxyl-terminated polyamidoamine dendrimer, denoted as PAMP, to create a potent inhibitor with a negatively charged hydrophobic surface. Results indicate that the PAMP with a proper degree of phenyl substitution (30-42%) alters the conformation of Aβ42 through both hydrophobic binding and electrostatic repulsive forces on its surface. With these well-balanced interactions, the inhibitor can even completely inhibit the formation of β-sheet structure of the peptide, accompanied by changes at the level of the fibrillary architecture. Moreover, the results also indicate that changes of Aβ42 aggregation pathway influenced by the PAMP occur at the very early stage, so the PAMP can significantly avoid the formation of toxic intermediates of Aβ42 aggregation |
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| Beschreibung: | Date Completed 04.02.2019 Date Revised 15.02.2019 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1520-5827 |
| DOI: | 10.1021/acs.langmuir.8b02890 |