Electrochemical approach for the aptamer-like conformational changes of α-synuclein peptides in the presence of copper(II)

• Published in: Electrochimica acta 2021-08, Vol.388, p.138534, Article 138534
• Main Authors: Li, Shaopei, Noroozifar, Meissam, Kerman, Kagan
• Format: Article
• Language: English
• Subjects: Antioxidants; Biosensors; Conformational change; Copper; Copper compounds; Copper(II); Electrochemical biosensor; Ethylenediaminetetraacetic acids; Ferrocene; Folding; Gold; Ions; Oligomerization; Oxidation; Parkinson's disease; Peptides; Photoelectrons; Pyrroloquinoline quinone; Quinones; Secondary ion mass spectrometry; Strong interactions (field theory); Surface properties; Time of flight photoelectron coincidence spectroscopy; X ray photoelectron spectroscopy; Zinc; α-Synuclein
• ISSN: 0013-4686; 1873-3859
• DOI: 10.1016/j.electacta.2021.138534

•Ferrocene-conjugated α-synuclein peptides were synthesized.•Square-wave voltammetry was applied to study the interaction between peptides and copper(II) ions.•The binding of copper(II) induced the folding of peptides increasing the ferrocene oxidation signal.•The interaction of zinc(II) with peptides did not cause a folding process on surfaces.•The binding of pyrroloquinoline quinone with peptides suppressed the folding process in the presence of copper(II) ions. The structure and aggregation states of alpha-synuclein (α-syn) have been shown to have a connection to the pathological development of Parkinson's disease (PD). Computational modeling studies have indicated that α-syn proteins misfold in the presence of biometals such as copper, iron and zinc, resulting in down-stream off-pathway oligomerization. If the early folding processes can be prevented, subsequent neurotoxicity due to the production of reactive oxygen species induced by the formation of α-syn-Cu(II) complexes can be suppressed. However, experimental data are lacking to support this hypothesis and many traditional approaches lack speed and sample volume efficiency. Through the application of an aptamer-like folding/unfolding strategy on an electrochemical platform, these challenges can be resolved. By exploiting the effect of spatial distance between the redox probe and electrode surface, a biosensor capable of monitoring the structural changes of α-syn peptides was constructed. Ferrocene-conjugated α-syn peptides (Fc-PEP) were immobilized on gold surfaces via gold-sulfur bond. Square-wave voltammetry (SWV) was used to monitor the Fc oxidation signal in the presence and absence of Cu(II). Full surface characterization studies were performed using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The results showed that Fc-PEPs folded in the presence of Cu(II), and this behaviour could be reversed with the addition of EDTA. The biosensor was able to demonstrate distinguishable current responses between the effects of Cu(II) and Zn(II) on the folding of Fc-PEPs. Finally, in the presence of a well-described antioxidant and amyloid inhibitor, pyrroloquinoline quinone (PQQ), the current responses remained the same, indicating the strong interaction between PQQ and Fc-PEPs that suppressed the folding process. Our preliminary results demonstrated that an aptamer-like electrochemical approach has a promising potential for developing a platform t