SCHEDULED MAINTENANCE
Enhancers of amyloid aggregation: novel ferrocene-based compounds selective toward amyloid models†
Abstract
Amyloid aggregation is at the molecular basis of neurodegeneration and provides toxic species which trigger the progression of the disease. Hence, there is an urgent need to identify novel molecules able to suppress toxicity either through an inhibitory or enhancing effect on aggregation. Herein, the effects of two metal complexes bearing a ferrocene unit and one or two propen-thyminyl groups, namely mono-T_Fc and di-T_Fc, on the aggregation properties of two different amyloid models were investigated. In detail, the peptide spanning residues 264–277 of the protein nucleophosmin 1 and that covering the C-terminal tail of the Aβ peptide (Aβ21–40) were chosen as amyloidogenic systems with different primary sequences and mechanisms of self-aggregation. UV–vis absorption spectroscopy, thioflavin T fluorescence assay and autofluorescence techniques were employed to evaluate the stability of mono-T_Fc and di-T_Fc and the effects of their presence on the aggregation of the investigated amyloidogenic peptides. The compounds selectively enhance the self-recognition of Aβ21–40 with a more marked effect exhibited by di-T_Fc, which contains two thymines. Scanning electron microscopy, dynamic light scattering and preliminary cell viability assays performed in SHSY5 cells confirm this result, which is due to the formation of metal-compound/peptide adducts as assessed by electrospray ionization mass spectrometry.
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