Antioxidant Promotion of Tyrosine Nitration in the Presence of Copper(II)

Copper(II) is known to catalyze the generation of reactive nitrogen species in the presence of hydrogen peroxide, nitrite or nitric oxide, leading to tyrosine nitration, a biomarker for free radical species associated diseases. Here, we find that biological antioxidants such as ascorbic acid can promote tyrosine nitration in the presence of copper(II) and nitrite under aerobic and weak acidic conditions. Tyrosine nitration is demonstrated on both β-amyloid peptide and angiotensin I. These studies show that i) ascorbic acid works as pro-oxidant in the presence of copper(II) to induce oxidation and nitration on peptides, ii) both free and coordinated copper(II) can catalyze peptide oxidation and nitration, iii) nitration occurs under mildly acidic conditions (pH = 6.0 - 6.5).