Effects of N-Methylated Amyloid-β30-40 Peptides on the Fibrillation of Amyloid-β1-40.
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.
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan.
Hirotsugu
H
Hiramatsu
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan.
Hironori
H
Ochiai
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan.
Tomoyuki
T
Komuro
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002850:Chromatography, Gel; D002942:Circular Dichroism; D008745:Methylation; D010446:Peptide Fragments / Q000378:metabolism*; D000685:Serum Amyloid A Protein; D013056:Spectrophotometry, Ultraviolet
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D000685:Serum Amyloid A Protein; C078592:amyloid beta-protein (1-40)
N-methylated peptide; ThT assay; amyloid β; correlation analysis; fibrillation inhibitor; monomer-dimer equilibrium