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Updated: May 27, 2026

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
Published on: May 22, 2018
Binding of inositol stereoisomers to model amyloidogenic peptides
Grace Li1, Sarah Rauscher, Stéphanie Baud
1Department of Biochemistry, University of Toronto, 27 King's College Circle, Toronto, Ontario, Canada M5S 1A1.
Abstract:
The self-aggregation of proteins into amyloid fibrils is a pathological hallmark of numerous incurable diseases such as Alzheimer's disease. scyllo-Inositol is a stereochemistry-dependent in vitro inhibitor of amyloid formation. As the first step to elucidate its mechanism of action, we present molecular dynamics simulations of scyllo-inositol and its inactive stereoisomer, chiro-inositol, with simple peptide models, alanine dipeptide (ADP) and (Gly-Ala)(4). We characterize molecular interactions and compute equilibrium binding constants between inositol and ADP as well as, successively, monomers, amorphous aggregates, and fibril-like β-sheet aggregates of (Gly-Ala)(4). Inositol interacts weakly with all peptide systems considered, with millimolar to molar affinities, and displaces the conformational equilibria of ADP but not of the (Gly-Ala)(4) systems. However, scyllo- and chiro-inositol adopt different binding modes on the surface of β-sheet aggregates. These results suggest that inositol does not inhibit amyloid formation by breaking up preformed aggregates but rather by binding to the surface of prefibrillar aggregates.
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