Cisplatin inhibits the formation of a reactive intermediate during copper-catalyzed oxidation of amyloid β peptide

Inorg Chem. 2014 Oct 6;53(19):10003-5. doi: 10.1021/ic5007764. Epub 2014 Sep 19.

Abstract

Cisplatin was studied for its effect on the copper-catalyzed oxidation of amyloid β (Aβ) peptide. The interaction of cisplatin with Aβ1-16 in the presence of Cu(II) was investigated using cyclic voltammetry and mass spectrometry. The positive shift in the E1/2 value of Aβ1-16-Cu(II) suggests that the interaction of cisplatin alters the copper-binding properties of Aβ1-16. The mass spectrometry data show complete inhibition of copper-catalyzed decarboxylation/deamination of the Asp1 residue of Aβ1-16, while there is a significant decrease in copper-catalyzed oxidation of Aβ1-16 in the presence of cisplatin. Overall, our results provide a novel mode by which cisplatin inhibits copper-catalyzed oxidation of Aβ. These findings may lead to the design of better platinum complexes to treat oxidative stress in Alzheimer's disease and other related neurological disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Catalysis
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • Copper / chemistry*
  • Humans
  • Molecular Structure
  • Oxidation-Reduction

Substances

  • Amyloid beta-Peptides
  • Copper
  • Cisplatin