Oxidation of Methionine Residues of Recombinant Human Interleukin 2 in Aqueous Solutions

Abstract

When recombinant human interleukin 2 (rIL-2) was stored for a long period in aqueous solutions, its methionine residues were spontaneously oxidized to the corresponding methionine sulfoxides. To clarify the oxidation process, rILr2 was treated with hydrogen peroxide, and three oxidation products were separated by reversed-phase high-performance liquid chromatography. By means of amino acid analyses after cyanogen bromide cleavage of these products, we found that Met104, Met23, and Met39 were consecutively oxidized in this order; Met46 was not oxidized easily. The substances generated by extended storage of rIL-2 in aqueous solutions were identified by comparison of their peptide maps with those of the chemically oxidized products. The protein-chemical properties of these products, except for the modifications of the methionine residues, were similar to those of intact rIL-2: their biological activities were almost the same. © 1989, The Pharmaceutical Society of Japan. All rights reserved.