Cyclen-hybrid compound captures copper to protect INS-1 cells from islet amyloid polypeptide cytotoxicity by inhibiting and lysing effects.

Human islet amyloid polypeptide (hIAPP) deposit is the hallmark of type 2 diabetes pathology. Here, we report that apo-cyclen, attached to a specific hIAPP recognition motif (NYGAIL), captured copper ions and became proteolytically active. This cyclen-NYGAIL-copper complex was able to interfere with hIAPP aggregation and cleave hIAPP. These activities rescued INS-1 cells from hIAPP induced cytotoxicity.