Assembly behavior of amylin fragment hIAPP19-37 regulated by Au(III) complexes.

Human islet amyloid polypeptide (hIAPP, amylin) may self-aggregate and rupture the membrane of β cells, which is closely correlated with the pathogenesis of type 2 diabetes mellitus (T2DM). Hence, suppressing amyloidogenic hIAPP may be beneficial for the treatment of diabetes. As an important part of hIAPP, the fragment hIAPP19-37 was studied in this work to explore their disaggregation and cellular behavior regulation by some selected Au complexes, as follows: dichloro diethyl dithiocarbamate Au complex [AuCl(DDTC)] (1), dichloro pyrrolidine dithiocarbamate Au complex [AuCl(PDT)] (2), dichloro 4-4'-dimethyl-2,2'-bipyridyl Au(III) chloride [AuCl(Me)bpy]Cl (3), and dichloro 4-4-di-tert-butyl-2,2'-bipyridyl Au(III) chloride [AuCl(t-Bu)bpy]Cl (4). The peptide aggregation was observed and analyzed by fluorescence assay, atomic force microscopy (AFM), dynamic light scattering (DLS) and other methods. The assembly behaviors of hIAPP19-37 affected by the four Au complexes indicated that these complexes could effectively inhibit the fibrillation of the peptide and depolymerized the aged peptide into nanoscale particles. These Au compounds also remarkably reduced membrane leakage and cytotoxicity caused by peptide oligomers. An interaction study revealed that the complexes were predominantly bound with hIAPP19-37 through hydrophobic and electrostatic interactions, and metal coordination. The differences among various complexes were compared according to their binding affinity, inhibitory effect, and cellular behavior. Our study offers a potential path for the possible utilization of Au compounds as amyloidosis inhibitors.