Constraints on the Structure of Fibrils Formed by a Racemic Mixture of Amyloid-β Peptides from Solid-State NMR, Electron Microscopy, and Theory.

ABSTRACT: Previous studies have shown that racemic mixtures of 40- and 42-residue amyloid-β peptides (d,l-Aβ40 and d,l-Aβ42) form amyloid fibrils with accelerated kinetics and enhanced stability relative to their homochiral counterparts (l-Aβ40 and l-Aβ42), suggesting a "chiral inactivation" approach to abrogating the neurotoxicity of Aβ oligomers (Aβ-CI). Here we report a structural study of d,l-Aβ40 fibrils, using electron microscopy, solid-state nuclear magnetic resonance (NMR), and density functional theory (DFT) calculations. Two- and three-dimensional solid-state NMR spectra indicate molecular conformations in d,l-Aβ40 fibrils that resemble those in known l-Aβ40 fibril structures. However, quantitative measurements of ¹³C-¹³C and ¹⁵N-¹³C distances in

SUBMITTER: Raskatov JA 

PROVIDER: S-EPMC8456612 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature