Unusual peroxidase activity of polynitroxylated pegylated hemoglobin: Elimination of H(2)O(2) coupled with intramolecular oxidation of nitroxides.

ABSTRACT

Polynitroxylated hemoglobin (Hb(AcTPO)(12)) has been developed as a hemoglobin-based oxygen carrier. While Hb(AcTPO)(12) has been shown to exert beneficial effects in a number of models of oxidative injury, its peroxidase activity has not been characterized thus far. In the blood stream, Hb(AcTPO)(12) undergoes reduction by ascorbate to its hydroxylamine form Hb(AcTPOH)(12). Here we report that Hb(AcTPOH)(12) exhibits peroxidase activity where H(2)O(2) is utilized for intramolecular oxidation of its TPOH residues to TPO. This represents an unusual redox-catalytic mechanism whereby reduction of H(2)O(2) is achieved at the expense of reducing equivalents of ascorbate converted into those of Hb(AcTPOH)(12), a new propensity that cannot be directly associated with ascorbate.