Anti-amyloidogenic hexapeptide-coated gold nanoparticles for enhanced inhibition of amyloid formation: A promising therapeutic approach

Under specific external stimulus, misfolded and natively disordered globular proteins undergo irreversible transformation into pathogenic β-sheet-rich insoluble fibrillar structure, and deposition of theses fibrils in cells and tissues leads to disorders like Alzheimer's, Dementia, Type II diabetes, and many more. Here, we have developed a positively-charged Arg-containing hexapeptide, SqP7, and elucidated its anti-amyloidogenic propensity on in vitro HEWL amyloid formation under acidic and neutral fibrillation conditions using computational tools and several biophysical techniques. SqP7, at a five-fold molar excess, displayed excellent amyloid inhibition capability at both pH conditions (~83 % and 72 % inhibition under acidic and neutral fibrillation conditions, respectively), and was further chosen as a coating agent on gold nanoparticles. This was done to investigate whether coating of this peptide on gold nanoparticles has any effect on its anti-amyloidogenic efficiency and effective inhibition concentration. The synthesized SqP7-coated gold nanoparticles were characterized to be spherical and highly-dispersed having a mean diameter of 9.12 ± 2.08 nm. The anti-amyloidogenic capability of the synthesized SqP7-coated gold nanoparticles was further evaluated, and a 10-fold reduction in the effective inhibition concentration of SqP7 was observed. This peptide‑gold nanoparticle based integrated approach can lead to the development of highly effective therapeutics for amyloid-related diseases, offering improved prevention and treatment options.