Inhibition of Amyloid-β Aggregation by Cobalt(III) Schiff Base Complexes: A Computational and Experimental Approach

Aysenur Iscen, Christopher R. Brue, Kaleigh F. Roberts, Joy Kim, George C. Schatz, Thomas J. Meade

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 novel cobalt(III) Schiff base complex with methylamine axial ligands, and we present both computational and experimental data demonstrating the reduction of β-sheet formation by this complex. The computations include molecular dynamics simulations of both monomeric and pentameric Aβ, which demonstrate decreased formation of β-sheet structures, destabilization of preformed β-sheets, and suppression of aggregation. These results are consistent with a dose dependence in experimental bulk aggregation data using thioflavin T fluorescence, and overall this study demonstrates useful drug activity of the cobalt complex.

Original languageEnglish
Pages (from-to)16685-16695
Number of pages11
JournalJournal of the American Chemical Society
Volume141
Issue number42
DOIs
Publication statusPublished - Oct 23 2019

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Schiff Bases
Cobalt
Amyloid
Agglomeration
Coordination Complexes
Molecular Dynamics Simulation
Histidine
Fluorescence
Ligands
Modulators
Molecular dynamics
Pharmaceutical Preparations
Computer simulation
thioflavin T
methylamine

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Inhibition of Amyloid-β Aggregation by Cobalt(III) Schiff Base Complexes : A Computational and Experimental Approach. / Iscen, Aysenur; Brue, Christopher R.; Roberts, Kaleigh F.; Kim, Joy; Schatz, George C.; Meade, Thomas J.

In: Journal of the American Chemical Society, Vol. 141, No. 42, 23.10.2019, p. 16685-16695.

Research output: Contribution to journalArticle

Iscen, Aysenur ; Brue, Christopher R. ; Roberts, Kaleigh F. ; Kim, Joy ; Schatz, George C. ; Meade, Thomas J. / Inhibition of Amyloid-β Aggregation by Cobalt(III) Schiff Base Complexes : A Computational and Experimental Approach. In: Journal of the American Chemical Society. 2019 ; Vol. 141, No. 42. pp. 16685-16695.
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