Role of the Metal Center in the Modulation of the Aggregation Process of Amyloid Model Systems by Square Planar Complexes Bearing 2-(2′-pyridyl)benzimidazole Ligands

Abstract

The effect of analogue Pd(II)-, Pt(II)-, and Au(III) compounds featuring 2-(2′-pyridyl)benzimidazole on the aggregation propensity of amyloid-like peptides derived from Aβ and from the C-terminal domain of nucleophosmin 1 was investigated. Kinetic profiles of aggregation were evaluated using thioflavin binding assays, whereas the interactions of the compounds with the peptides were studied by UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. The results indicate that the compounds modulate the aggregation of the investigated peptides using different mechanisms, suggesting that the reactivity of the metal center and the physicochemical properties of the metals (rather than those of the ligands and the geometry of the metal compounds) play a crucial role in determining the anti-aggregation properties.

Keywords

• amyloid aggregation
• metallodrugs
• gold(iii) compounds
• platinum(ii) compounds
• palladium(ii) compounds
• anti-aggregation properties