title: Conjugates of superoxide dismutase with the Fc fragment of immunoglobulin G.
abstract: We constructed conjugates of superoxide dismutase (SOD) and the Fc fragment of human immunoglobulin G. The lysyl residues of bovine erythrocyte Cu,Zn-SOD were covalently linked with cysteine residues of the Fc fragment using N-succinimidyl 4-(N-maleimido)-butylate as a crosslinking agent. Analysis by gel filtration and SDS-PAGE revealed that the conjugates were composed of one molecule of SOD linked with one molecule of Fc [SOD-(Fc)1] and one SOD molecule linked with several Fc molecule [SOD-(Fc)n]. The resulting SOD-Fc conjugates retained more than 90% of the enzyme activity of SOD. When those conjugates were administered intravenously to mice, the half-lives of SOD activity in the circulation were 29 and 42 h for SOD-(Fc)1 and SOD-(Fc)n, respectively, while free SOD had a half-life of 5 min. Intravenous administration of the conjugates to mice markedly repressed the increase in serum glutamic-oxaloacetic transaminase (GOT) activity induced by paraquat. These results suggest that SOD-Fc conjugates, which have long half-lives, effectively perform dismutation of superoxide radicals and may be useful for preventing tissue injury caused by hazardous oxygen metabolites.
authors.affiliation: Teijin Institute for Biomedical Research, Tokyo.
authors.forename: A
authors.initials: A
authors.lastname: Zanma
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Masuho
mesh_terms: D000818:Animals; D006207:Half-Life; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000302:isolation & purification* / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000302:isolation & purification* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D010269:Paraquat / Q000633:toxicity; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000302:isolation & purification* / Q000493:pharmacokinetics; D013481:Superoxides / Q000378:metabolism
chemical_list: D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D013481:Superoxides; D013482:Superoxide Dismutase; D010269:Paraquat