Human serum albumin incorporating synthetic hemes as an O2-carrying hemoprotein: control of O2-binding ability by heme structure

Incorporation of different structured synthetic hemes, 5,10,15,20-tetraphenylporphyrinatoiron(II) derivetives with a covalently linked proximal base [FeP( 1 ) to FeP( 7 )], into human serum albumin (HSA), provides seven types of albumin-heme hybrids (HSA-FeP) with different O₂-binding abilities. An HSA host absorbs a maximum of eight FeP molecules in each case. The obtained all HSA-FePs can reversibly bind and release O₂ under physiological conditions (in aqueous media, pH 7.3, 37°C) as similar as hemoglobin and myoglobin. The difference in the fence structures did not affect the O₂-binding parameters, however the axial histidine coordination significantly increased the O₂-binding affinity, which is ascribed to the low O₂-dissociation rate constants. The most remarkable effect of the heme structure appeared in the half-lifetime (τ_1/2) of the O₂-adduct complex. The dioxygenated rHSA-FeP( 4 ) showed an unusually long lifetime (τ_1/2: 25 hr at 37°C) which is ca. 13-fold longer than that of rHSA-FeP( 1 ).     

Oxygen-carrying plasma hemoprotein “albumin-heme”: nitric oxide binding and physiological responses after administration in vivo

Recombinant human serum albumin complexed with tetraphenylporphinatoiron(II) derivative, “albumin-heme (rHSA-FeP)”, is a synthetic oxygen (O₂)-carrying plasma hemoprotein, which becomes a new class of red blood cell substitute. The UV-vis. absorption and ESR spectroscopy revealed that rHSA-FeP formed six-coordinate nitrosyl complex after exposure of nitric oxide (NO) gas. Although the NO-binding affinity of rHSA-FeP (P_1/2^NO: 1.7 × 10⁻⁶ Torr, pH 7.3, 25°C) is 9-fold higher compared to that of hemoglobin (Hb), the administration of this artificial hemoprotein solution into anesthetized rat does not induce an acute increase in blood pressure (hypertension), which is often observed in Hb-based O₂-carriers due to the depletion of NO (endothelial derived relaxing factor).