Preparation of a polyethylene glycol: superoxide dismutase adduct, and an examination of its blood circulation life and anti-inflammatory activity

Abstract

Methoxypolyethylene glycol (PEG) of 5000 daltons was attached covalently to 19 of the 20 available lysine residues of bovine erythrocyte superoxide dismutase. The adduct (PEG-superoxide dismutase) has 51% of the enzymatic activity of superoxide distmutase. PEG-superoxide dismutase exhibits a sharply enhanced serum circulating life during repetitive intravenous injections compared to the native enzyme. While no evidence of an immune response to repetitive injections of PEG-superoxide dismutase is observed, the unmodified enzyme appears to produce slight sensitization in the form of quicker removal from the serum after 13 injections over a period of 30 days. Antisera to superoxide dismutase and PEG-superoxide dismutase, however, produce no detectable antibodies as determined by the Ouchterlony method. Intraperitoneally injected PEG-superoxide dismutase enters the bloodstream more readily than superoxide dismutase. PEG modification slightly improves the enzyme's anti-inflammatory activity, which was observed in rats over a period of eight days.