Effects of N-Methylated Amyloid-β30-40 Peptides on the Fibrillation of Amyloid-β1-40

Hirotsugu Hiramatsu, Hironori Ochiai, Tomoyuki Komuro

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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 languageEnglish
Pages (from-to)425-433
Number of pages9
JournalChemical Biology and Drug Design
Volume87
Issue number3
DOIs
Publication statusPublished - 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

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