title: Electrochemical "signal-on" reporter for amyloid aggregates.
abstract: 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).
authors.affiliation: Department of Physical and Environmental Sciences, University of Toronto at Scarborough, Toronto, Ontario, Canada.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Beheshti
authors.forename: Sanela
authors.initials: S
authors.lastname: Martić
authors.forename: Heinz-Bernhard
authors.initials: HB
authors.lastname: Kraatz
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D055664:Electrochemical Techniques; D004566:Electrodes; D005296:Ferrous Compounds / Q000737:chemistry*; D006046:Gold / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D000075163:Metallocenes; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D005296:Ferrous Compounds; D000075163:Metallocenes; D010446:Peptide Fragments; D010455:Peptides; C092395:amyloid beta-protein (12-28); D006046:Gold; C004998:ferrocene