Ferrocene Derived Peptide Synthesis, Characterization And The Interaction With Beta-amyloid

In this study, two title compounds were synthesized from ferrocence: (1) Ferrocenyl tripeptides (compound 10, GPR-Fca, Boc-Gly-Pro-Arg(NO₂)-Fc-COOMe, yield 7.25%); (2) Ferrocenyl pentapeptides (compound 17, Fc-iAβ5, Fc-Leu-Pro-Phe-Phe-Asp(OMe)-OMe, yield 17.86%). And two typical inhibitors forβ-amyloid peptide was synthesized by peptide synthesis: (3) tripeptides (compound 11, GPR, Boc-Gly-Pro-Arg(NO₂)-OMe); (4) pentapeptides (compound 19, iAβ5, Ac-Leu-Pro-Phe-Phe-Asp-OH). The IR spectrum, UV-vis spectrum, ¹H NMR and mass spectrum were recorded in each step to characterize the compounds.Atomic force microscopy(AFM), thioflavin T (ThT) fluorescence spectroscopy and electrochemical methods were used to investigate the interaction betweenβ-amyloid (Aβ₄₂) and each Aβinhibitor in vitro. In light of AFM results, the presence of GPR-Fca inhibits Aβ₄₂ fibrils aggregate formation greatly in vitro, which proved that there is of great binding capacity between GPR-Fca and Aβ₄₂. As evidenced in vitro by ThT fluorescence method, GPR-Fca inhibits Aβ₄₂ fibrillogenesis more strongly than GPR itself, and 5 M GPR-Fca is the best for inhibition and disassembly of Aβ₄₂ fibrils. Meanwhile, electrochemical methods were used to quickly investigate the interaction between GPR-Fca and Aβ₄₂ in vitro. As evidenced in vitro by AFM, the results confirmed that iAβ5 is a typical oligopeptide inhibitor for Aβ₄₂ and is able to inhibit and disaggregate Aβ₄₂ fibrillogenesis. By ThT fluorescence method in vitro, The experiment results showed that Fc-iAβ5 inhibits Aβ₄₂ fibrillogenesis more strongly than iAβ5 itself. Moreover, Fc-iAβ5 is able to partially disaggregate performed fibrils.