Coordination complexes have emerged as prominent modulators of amyloid aggregation via their interaction with the N-terminal histidine residues of amyloid-β (Aβ). Herein we report the synthesis and characterization of a cobalt(III) Schiff base complex (Co(III)-sb) capable of inhibiting Aβ aggregation. We present both computational and experimental studies demonstrating the reduction of β-sheet structures as the primary mechanism of inhibition. Computational analysis using molecular dynamics simulations of both monomeric and pentameric Aβ proteins reveal that in the presence of the Co(III)-sb complex there is significantly decreased formation of β-sheet structures, destabilization of preformed β-sheets, and suppression of aggregation. These results are consistent with a dose dependence addition of Co(III)-sb complexes in experimental bulk aggregation studies using thioflavin T fluorescence and Atomic Force Microscopy. Modification of the Co(III)-sb with a targeting moiety for increased binding affinity demonstrate increased inhibition of β-sheet structures in molecular dynamics simulations. The characterization of the effect of Co(III)-sb complexes on the thermodynamics of Aβ folding using replica exchange molecular dynamics will be discussed.

Inhibition of amyloid-β aggregation by cobalt(III) Schiff base complexes: Computational and experimental approach

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.