Systhesis And Characterization Of Fluorescent Naphthalimide-peptide And Electrochemical Ferrocene-peptide As Well As Their Interaction With Aβ₄₂

One of the most prominent neuropathological hallmarks in the brains of Alzheimer’s disease(AD) patients is the deposition of senil e plaques, these plaques are extracellular lesions that are primarily composed of β-amyloid(Aβ). The research in recent years shows tha t soluble Aβ oligomers are more toxic in vitro and in vivo than fib rils and may represent the primary pathological species, instead fibri1s may play a protective effect on nerve cells. Two peptide derivati ves Naph-Lys-Gly-Lys-Leu-Val-Phe-Phe-Gly-Lys-COOH and Fc-Lys-G ly-Lys-Leu-Val-Phe-Phe-Gly-Lys-COOH were designed and synthesize d which have contrary effection on the aggregation of Aβ, the form er obvious promoted Aβ fibril formation, by contrast, the latter inhi bited Aβ aggregation.(Naph:1,8-naphthalimide; Fc:ferrocenoyl; Ac: acetyl)Fluorescent peptide Naph-KGKLVFFGK, Electrochemical peptid e Fc-GKLVFFGK and control peptide Ac-GKLVFFGK were synthes ized from1,8-naphthalimide, ferrocene monocarboxylic acid, Gly, Ph e, Leu, Val, and Lys by solid-phase peptide synthesis method using O-(benzotriazol-yl)-N,N,N,N-tetramethyluronium(HBTU)/1-hydroxyben zotrizole(HOBt) as coupling reagents, and then characterized by IR, UV, NMR and MS. All three peptides were purified and analysed u sing HPLC, the retention times were10.5,12.8and12.8min respec tively, the purity of all three peptides was all above99.5%. The sp ectrographic results showed that the maximum absorption and emissi on wavelength of Naph-KGKLVFFGK are344nm and400nm respec tively; the electrochemical results showed that Fc-KGKLVFFGK exh ibits a pair of well-defined voltammetric peaks with oxidation poten tial(Ea) and reduction potential(Ec) at0.534V and0.443V in the ra nge of0.2-0.TV, and the ratio of oxidative to reductive peak curren t is1.14.Atomic force microscopy (AFM), Thioflavine T fluorescence sp ectroscopy(ThT), Dynamic light scattering(DLS) and electrochemical methods were employed to investigate the interaction between theset hree peptides and Aβ42. The experimental results demonstrated thatN aph-KGKLVFFGK obvious promoted Aβ42aggregation, while theagg regation of Aβ42was inhibited by both Fc-KGKLVFFGK and Ac-K GKLVFFGK, the former displayed more apparent effect, all three of the peptides contain a pentapeptide KLVFF, which serves as an eff ective recognition element, and We postulate that naphthalimide may combine with Aβ42and promote Aβ42fibrillization by aromaticstac king or hydrophobic forces, moreover ferrocene may insert into β-s heet structures and inhibit Aβ42fibrillization by its lipophicityandspa ce steric hindrance.