In vitro binding of propranolol and progesterone to native and desialylated human orosomucoid

Abstract

A comparison of propranolol and progesterone binding to native and desialylated human orosomucoid was studied by means of equilibrium dialysis. The association constants of propranolol and progesterone binding to native human orosomucoid under physiological conditions were 8.4 × 10⁵ and 3.2 × 10⁵ M⁻¹, respectively. Enzymatic desialylation of human orosomucoid removed 95% of the sialic acid content and reduced the binding affinity of propranolol from 8.4 × 10⁵ to 6.0 × 10⁵ M⁻¹, but the affinity of progesterone was not affected. In addition, desialylation reduced the percent binding for propranolol, indicating that electrostatic attraction of the positive charge on propranolol by sialic acid residues on human orosomucoid had some effect on the binding ability of purified orosomucoid for propranolol. The present data suggest that the electrostatic attraction between sialic acid and propranolol is partially responsible for the preferential binding of basic drugs to orosomucoid in plasma.