A new class of aggregation inhibitor of amyloid-β peptide based on an O-acyl isopeptide.

Authors :: Kawashima H
Sohma Y
Nakanishi T
Kitamura H
Mukai H
Yamashita M
Akaji K
Kiso Y
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2013 Nov 01; Vol. 21 (21), pp. 6323-7. Date of Electronic Publication: 2013 Sep 07.
Publication Year :: 2013
Abstract: Inhibition of amyloid β peptide (Aβ) aggregation is a potential therapeutic approach to treat Alzheimer's disease. We report that an O-acyl isopeptide of Aβ1-42 (1) containing an ester bond at the Gly(25)-Ser(26) moiety inhibits Aβ1-42 fibril formation at equimolar ratio. Inhibitory activity was retained by an N-Me-β-Ala(26) derivative (2), in which the ester of 1 was replaced with N-methyl amide to improve chemical stability at physiological pH. Inhibition was verified by fluorescence anisotropy, Western blot, and atomic force microscopy. This report suggests a new class of Aβ aggregation inhibitor based on modification of Aβ1-42 at Gly(25)-Ser(26).<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Subjects :: Amino Acid Sequence
Amyloid beta-Peptides chemistry
Amyloid beta-Peptides metabolism
Esters
Fluorescence Polarization
Microscopy, Atomic Force
Molecular Sequence Data
Peptides chemical synthesis
Peptides metabolism
Protein Binding
Amyloid beta-Peptides antagonists & inhibitors
Peptide Fragments chemistry
Peptides chemistry

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