Modulation of amyloid-β aggregation by histidine-coordinating cobalt(III) schiff base complexes

Marie Heffern, Pauline T. Velasco, Lauren M. Matosziuk, Joseph L. Coomes, Constantine Karras, Mark A. Ratner, William L. Klein, Amanda L. Eckermann, Thomas J. Meade

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Oligomers of the Aβ42 peptide are significant neurotoxins linked to Alzheimer's disease (AD). Histidine (His) residues present at the N terminus of Aβ42 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 Aβ toxicity have emerged as therapeutic candidates. Cobalt(III) Schiff base complexes (Co-sb) were evaluated for their ability to interact with Aβ peptides. HPLC-MS, NMR, fluorescence, and DFT studies demonstrated that Co-sb complexes could interact with the His residues in a truncated Aβ16 peptide representing the Aβ42 N terminus. Coordination of Co-sb complexes altered the structure of Aβ42 peptides and promoted the formation of large soluble oligomers. Interestingly, this structural perturbation of Aβ correlated to reduced synaptic binding to hippocampal neurons. These results demonstrate the promise of Co-sb complexes in anti-AD therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)1584-1589
Number of pages6
JournalChemBioChem
Volume15
Issue number11
DOIs
StatePublished - Jul 21 2014
Externally publishedYes

Fingerprint

Schiff Bases
Cobalt
Histidine
Amyloid
Agglomeration
Modulation
Oligomers
Toxicity
Alzheimer Disease
Oligomerization
Aptitude
Coordination Complexes
Neurotoxins
Discrete Fourier transforms
Neurons
Transition metals
Metal ions
Fluorescence
Metals
Binding Sites

Keywords

  • Alzheimer's disease
  • amyloid beta
  • cobalt
  • histidine
  • oligomers

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Cite this

Heffern, M., Velasco, P. T., Matosziuk, L. M., Coomes, J. L., Karras, C., Ratner, M. A., ... Meade, T. J. (2014). Modulation of amyloid-β aggregation by histidine-coordinating cobalt(III) schiff base complexes. ChemBioChem, 15(11), 1584-1589. https://doi.org/10.1002/cbic.201402201

Modulation of amyloid-β aggregation by histidine-coordinating cobalt(III) schiff base complexes. / Heffern, Marie; Velasco, Pauline T.; Matosziuk, Lauren M.; Coomes, Joseph L.; Karras, Constantine; Ratner, Mark A.; Klein, William L.; Eckermann, Amanda L.; Meade, Thomas J.

In: ChemBioChem, Vol. 15, No. 11, 21.07.2014, p. 1584-1589.

Research output: Contribution to journalArticle

Heffern, M, Velasco, PT, Matosziuk, LM, Coomes, JL, Karras, C, Ratner, MA, Klein, WL, Eckermann, AL & Meade, TJ 2014, 'Modulation of amyloid-β aggregation by histidine-coordinating cobalt(III) schiff base complexes', ChemBioChem, vol. 15, no. 11, pp. 1584-1589. https://doi.org/10.1002/cbic.201402201
Heffern, Marie ; Velasco, Pauline T. ; Matosziuk, Lauren M. ; Coomes, Joseph L. ; Karras, Constantine ; Ratner, Mark A. ; Klein, William L. ; Eckermann, Amanda L. ; Meade, Thomas J. / Modulation of amyloid-β aggregation by histidine-coordinating cobalt(III) schiff base complexes. In: ChemBioChem. 2014 ; Vol. 15, No. 11. pp. 1584-1589.
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