Purification, modification, physico-chemical and pharmacokinetic characterization of arginase, an enzyme of potential use in therapy.

Beef liver arginase, an enzyme potentially useful in the therapy of arginine dependent tumors or of familial hyperargininemia, was purified to homogeneity by a procedure involving a key step of hydrophobic affinity chromatography. The enzyme was extensively modified by the covalent linking of monomethoxypolyethyleneglycol molecules according to a procedure recently proposed by the Authors (Veronese et al., Appl. Biochem. Biotecnol. 11, 869, 1985) without any significant loss of activity. The derivative enzyme presents more convenient properties for a therapeutic use, as compared to the native enzyme, such an increased structural stability, a decreased digestion by proteolytic enzymes and an expanded clearance time in rats.