Abstract
Alzheimer's disease is a neurodegenerative disorder associated with amyloid-β (Aβ) fibrillation. N-Methylated amyloid-β peptides are potent inhibitors of amyloid-β fibrillation. We investigated the inhibitory effect of N-Methylated Aβ30-40 peptides on Aβ1-40 fibrillation. N-Methylated Aβ30-40 peptides affected the fibrillation, and this effect was dependent on the concentration of N-Methylated peptide and the number and position of N-Methylated groups. N-Methylated Aβ30-40 peptides were co-aggregated with Aβ1-40. Spectroscopic technique was adopted to investigate an origin of the observed dependence. Suppression of thioflavin T (ThT) fluorescence count was correlated with the dissociation constant Kd of monomer-dimer equilibrium of each N-Methylated Aβ30-40 peptide. Monomeric N-Methylated peptides decreased ThT fluorescence count during Aβ1-40 fibrillation. Secondary structure content was not largely different between Aβ1-40 fibrils and co-aggregates. These results suggested that N-Methylated Aβ30-40 peptides disrupted the regular β-sheet structure of Aβ1-40 fibrils and affected the ThT fluorescence count. The monomer-dimer equilibrium of N-Methylated peptides was (partly) responsible for the observed dependence of their inhibitory effect on the concentration of N-Methylated peptide and the number and position of N-Methylated groups. Our study provides a hint to design new N-Methylated inhibitor peptides of fibrillation.
Original language | English |
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Pages (from-to) | 425-433 |
Number of pages | 9 |
Journal | Chemical Biology and Drug Design |
Volume | 87 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2016 Mar |
Keywords
- N-methylated peptide
- ThT assay
- amyloid β
- correlation analysis
- fibrillation inhibitor
- monomer-dimer equilibrium
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Pharmacology
- Drug Discovery
- Organic Chemistry