Inhibition of peroxynitrite-induced dityrosine formation with oxidized and reduced thiols, nitric oxide donors, and purine derivatives.

Peroxynitrite, formed by the combination of superoxide anion and nitric oxide, is a powerful oxidant at physiological pH and is apparently involved in the pathogenesis of several human diseases. Therefore, inhibitors of peroxynitrite-induced oxidation are important targets for pharmaceutical development. The reaction of peroxynitrite with L-tyrosine, one of its biological targets, yields stable products, including nitrotyrosine and dityrosine. Here we test the ability of thiols, nitric oxide donors, and purine derivatives to inhibit peroxynitrite-induced dityrosine formation in a physiological buffer containing bicarbonate/CO2. We show that both reduced and oxidized thiols, nitric oxide donors, and urate, but not other purine derivatives, reduce peroxynitrite-induced dityrosine formation.