Synthesis of Polymeric Reconstituted Hemoglobins as Superoxide Dismutase Mimics Designed for Long-term Circulation Maintenance

Abstract

Superoxide dismutase (SOD), catalase and glutathione peroxidase catalize the elimination of reactive oxygen species (ROS) such as a superoxide anion radical (O₂^-·). But enzyme activity decreases in diseases in which ROS attacks DNA, lipid and blood vessels. Recent studies on SOD mimics indicate that manganese porphyrin (MnT2MePyP) express high SOD activity. But the half-life of MnT2MePyP in the blood is usually very short. In the present study, a novel reconstituted polymerized hemoglobin containing manganese porphyrins (MnT2MePyP-PolyHb) was synthesized. SOD activity of MnT2MePyP-PolyHb (IC₅₀ = 1.1 μM, k_cat = 7.3 × 10⁶ M^-1s^-1) was found to be somewhat less than that of MnT2MePyP (IC₅₀ = 0.23 μM, k_cat = 60 × 10⁶ M^-1s^-1). MnT2MePyP-PolyHb half-life in H₂O₂ (t_1/2 = 1070 s) was found to be as much as four times that of MnT2MePyP (t_1/2 = 250 s). MnT2MePyP-PolyHb may thus be a valid SOD model for effectively maintaining and prolonging blood circulation.