MECHANISTIC STUDIES OF PEROXYNITRITE BIOCHEMISTRY

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DESCRIPTION: This is a proposal to develop methods to synthesize stable peroxynitrite salts in pure form and to study the fundamental chemistry of peroxynitrite and its reactions with biological molecules. Peroxynitrite is a highly reactive reaction product of nitric oxide and superoxide that is thought to mediate biological oxidative damage where these precursors are formed together. Mechanistic studies of peroxynitrite chemistry have been hindered by the difficulty of obtaining peroxynitrite of high purity. This proposal builds upon Dr. Bohle's recent success in synthesizing tetramethylammonium peroxynitrite in pure crystalline form. Dr. Bohle proposes 1) work to optimize the synthetic method and to adapt it for synthesizing heavy metal peroxynitrite salts; 2) spectroscopic characterization of the salts and studies of peroxynitrite decomposition mechanisms in solution; 3) studies of the reaction of peroxynitrite with phospholipids; 4) mechanistic studies of the inactivation of sulfhydryl proteases by nitrogen oxides and peroxynitrite; 5) identification of potential markers products for peroxynitrite reactions with antioxidants; and 6) identification of products of nucleic acid modification by peroxynitrite.