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

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 E_1/2 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.