Skip to main content

Modification of Aβ Peptide Aggregation via Covalent Binding of a Series of Ru(III) Complexes

Resource type
Date created
2019-12-03
Authors/Contributors
Abstract
Alzheimer's disease (AD) is the most common form of dementia, leading to loss of cognition, and eventually death. The disease is characterized by the formation of extracellular aggregates of the amyloid-beta (Aβ) peptide and neurofibrillary tangles of tau protein inside cells, and oxidative stress. In this study, we investigate a series of Ru(III) complexes (Ru-N) derived from NAMI-A in which the imidazole ligand has been substituted for pyridine derivatives, as potential therapeutics for AD. The ability of the Ru-N series to bind to Aβ was evaluated by NMR and ESI-MS, and their influence on the Aβ peptide aggregation process was investigated via electrophoresis gel/western blot, TEM, turbidity, and Bradford assays. The complexes were shown to bind covalently to the Aβ peptide, likely via a His residue. Upon binding, the complexes promote the formation of soluble high molecular weight aggregates, in comparison to peptide precipitation for peptide alone. In addition, TEM analysis supports both amorphous and fibrillar aggregate morphology for Ru-N treatments, while only large amorphous aggregates are observed for peptide alone. Overall, our results show that the Ru-N complexes modulate Aβ peptide aggregation, however, the change in the size of the pyridine ligand does not substantially alter the Aβ aggregation process.
Document
Published as
Gomes LMF, Bataglioli JC, Jussila AJ, Smith JR, Walsby CJ and Storr T (2019) Modification of Aβ Peptide Aggregation via Covalent Binding of a Series of Ru(III) Complexes. Front. Chem. 7:838. DOI: 10.3389/fchem.2019.00838.
Publication title
Front. Chem.
Document title
Modification of Aβ Peptide Aggregation via Covalent Binding of a Series of Ru(III) Complexes
Date
2019
Volume
7
Issue
838
Publisher DOI
10.3389/fchem.2019.00838
Copyright statement
Copyright is held by the author(s).
Scholarly level
Peer reviewed?
Yes
Language
English
Member of collection
Download file Size
fchem-07-00838.pdf 1.1 MB

Views & downloads - as of June 2023

Views: 11
Downloads: 0