Electrochemical “Signal‐On” Reporter for Amyloid Aggregates

The synthesis and characterization of four new Ferrocene (Fc) bioconjugates, bearing a podant (Lys)‐Leu‐Val‐Phe‐Phe motif, namely the hydrophobic sequence of amyloid‐β‐peptides (Aβ), is reported. The Fc‐peptide conjugates are characterized by a reversible redox activity and the ability to undergo hydrophobic and hydrogen bonding interactions. Biomolecular interactions between Fc‐bioconjugates with Aβ 12–28 fragments were studied by circular dichroism (CD), transmission electron microscopy (TEM), and electrochemistry. All four Fc‐peptides interacted favourable with Aβ 12–28 and prevented fibril formation, the extent of which depended on the length of the peptide and the nature of the C‐terminal group. The aggregates obtained for the Aβ 12–28 /Fc‐peptide mixtures range from short fibrils to spherical aggregates. We demonstrated that in solution the peptide sequence and peptide charge affect the biomolecular interactions. Fc‐peptide interactions with immobilized Aβ 12–28 ‐ Cys films on Au surfaces were detected by measuring the current response of the Fc redox process. The formal redox potential, E 0 , at ∼440 (10) mV and i pc / i pa at 0.9 were observed characteristic for the monosubstituted Fc‐derivative undergoing a one‐electron redox process. On the surface, methyl ester‐protected Fc‐peptides ( 1 and 3 ) interacted only weakly with Aβ 12–28 ‐Cys films, giving rise to minimal redox activity. In contrast, charged Fc‐peptides ( 2 and 4 ) gave a significant electrochemical readout following the interaction with Aβ 12−28 ‐ Cys films. Interestingly, the Fc‐peptide charge dictates the surface‐assisted interactions, while hydrophobic and ionic effects contribute to the overall solution behaviour of the Fc‐bioconjugates with Aβ 12–28 .