Title

Modulation of Amyloid-β Aggregation by Histidine-Coordinating Cobalt(III) Schiff Base Complexes

Document Type

Article

Publication Date

2014

Publication Source

ChemBioChem

Volume Number

15

Issue Number

11

First Page

1584

Last Page

1589

ISSN

1439-7633

Abstract

Oligomers of the A beta 42 peptide are significant neurotoxins linked to Alzheimer's disease (AD). Histidine (His) residues present at the N terminus of A beta 42 are believed to influence toxicity by either serving as metal-ion binding sites (which promote oligomerization and oxidative damage) or facilitating synaptic binding. Transition metal complexes that bind to these residues and modulate A beta toxicity have emerged as therapeutic candidates. Cobalt(III) Schiff base complexes (Co-sb) were evaluated for their ability to interact with A beta peptides. HPLC-MS, NMR, fluorescence, and DFT studies demonstrated that Co-sb complexes could interact with the His residues in a truncated A beta 16 peptide representing the A beta 42 N terminus. Coordination of Co-sb complexes altered the structure of A beta 42 peptides and promoted the formation of large soluble oligomers. Interestingly, this structural perturbation of A beta correlated to reduced synaptic binding to hippocampal neurons. These results demonstrate the promise of Co-sb complexes in anti-AD therapeutic approaches.

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