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

Chem Commun (Camb). 2010 Nov 14;46(42):8023-5. doi: 10.1039/c0cc02555k. Epub 2010 Sep 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Copper / chemistry*
  • Cyclams
  • Heterocyclic Compounds / chemistry*
  • Humans
  • Islet Amyloid Polypeptide / toxicity*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Cyclams
  • Heterocyclic Compounds
  • Islet Amyloid Polypeptide
  • Copper
  • cyclen