Regulation of the aggregation behavior of human islet amyloid polypeptide fragment by titanocene complexes

Weihong Du, Gehui Gong, Wenji Wang, Jufei Xu

The aggregation of human islet amyloid polypeptide (hIAPP) is associated with type II diabetes. The misfolding of hIAPP induces amyloid deposition and causes β-cell dysfunction. Metal complexes are potential metallodrugs that may reverse the aggregation of amyloid peptides. hIAPP19-37 is a crucial fragment of the full-length hIAPP1-37 and contains typical aromatic residues and a core hydrophobic region. In this work, we studied the effects of titanocene complexes titanocene dichloride (1), titanocene salicylic acid complex (2), and titanocene methionine complex (3) on the aggregation behavior of hIAPP19-37. We also explored the possible interactions of these complexes with hIAPP19-37. Results demonstrated that the titanocene complexes could effectively inhibit the aggregation of hIAPP19-37. The complexes bound with hIAPP19-37 in a spontaneous and exothermic process through hydrophobic interaction. Moreover, complex 3 could significantly decrease the cytotoxicity of hIAPP19-37 and improve cell survival. These data provide a basis for the use of titanocene complexes as potential agents against amyloidosis.