Human Serum Albumin Incorporating Synthetic Hemes as an O_2-Carrying Hemoprotein: Control of O_2-Binding Ability by Heme Structure

摘要

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 O_2 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 O_2-binding parameters, however the axial histidine coordination significantly increased the O_2-binding affinity, which is ascribed to the low O_2-dissociation rate constants. The most remarkable effect of the heme structure appeared in the half-lifetime (τ_(1/2)) of the O_2-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).