Electrochemical Activity Of Ferrocene - Peptide Synthesis, Characterization Of Beta-amyloid Peptide Aggregation Inhibitory Activity

The aggregation of (β-amyloid peptide (Aβ) in the brain is the main pathological trait of Alzheimer's disease. The inhibition of Aβaccumulation can slow down or prevent the disease. Pentpeptide KLVFF is a typical inbibitor for Aβaggregation. However, the low hydropholity and lipophilic property, and low anti-enzymatic stability limit its using as an Aβinhibitor. Many works have done to improve its properties. In this study, hydrophilic amino acids and lipophilic ferrocence moiety were attached at both C-and N-terminal of KLVFF.Fc-Gly-Lys-Leu-Val-Phe-Phe-Gly-Lys-OH(Fc-GKLVFFGK,Fc:ferroc enoyl) was synthesized from ferrocene monocarboxylic acid, Gly, Phe, Leu, Val, and Lys by solid-phase peptide synthesis method using O-(benzotriazol-yl)-N,N,N',N'-tetramethyluronium(HBTU)/1-hydroxybe nzotrizole (HOBT) as coupling reagents with yield of 45.6%.The crude peptide was purified using HPLC. The title peptide, Fc-Gly-Lys-Leu-Val-Phe-Phe-Gly-Lys-OH (Fc-GKLVFFGK), was then characterized by IR, UV, NMR and MS. The voltammetric method was employed to determine the electrochemical properties of the title compound. The electrochemical results showed that the title compound exhibit a pair of well-defined redox wave at oxidation potential (Ea) and reduction potential (Ec) at 0.464 V and 0.396 V, respectively, in therange of 0.2-0.7V, and the ratio of Ipa and Ipc is 1.07. Thioflavine T fluorescence spectroscopy, Atomic force microscopy (AFM) and electrochemical methods were employed to investigate the interaction between Fc-GKLVFFGK and Aβ1-42.Especially, Fc-GKLVFFGK is able to partially disaggregate performed fibrils as well. The experimental results showed that the inhibitory effect is better than that of KLVFF.