Effects of gold complexes on the assembly behavior of human islet amyloid polypeptide

Human islet amyloid polypeptide (hIAPP) is a well-known amyloid protein that is associated with type II diabetes. Inhibitors of this peptide include aromatic organic molecules, short peptides, and metal complexes, such as zinc, ruthenium and vanadium compounds. Various metal ions and their complexes affect the fibrillization of hIAPP in different action modes. However, the assembly mechanism of the peptide remains unclear. This study evaluated the inhibitory effects of three gold complexes with different nitrogen-containing aromatic ligands, namely, [Au(bipy)Cl2][PF6] (1), [Au(Ph2bpy)Cl2]Cl (2), and [Au(phen)Cl2]Cl (3), on the amyloid fibrillization of hIAPP. The complexes interacted with the peptide mainly through hydrophobic interaction and metal coordination. The concentration dependence of hIAPP aggregation on gold complex indicated that the assembly behavior of hIAPP is significantly affected by these compounds. The gold complexes inhibited peptide aggregation through dimerization and stabilized the peptide to monomers. Gold ion was found to be a key influencing factor of the binding mode and assembly behavior of hIAPP. The different effects of the complexes on peptide aggregation might be attributed to their special ligands. This study provided insights into the inhibitory mechanism of gold complexes against hIAPP fibrillization.