Conjugates of superoxide dismutase with the Fc fragment of immunoglobulin G.
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.
Zanma
A
A
Teijin Institute for Biomedical Research, Tokyo.
Matsumoto
Y
Y
Masuho
Y
Y
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
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D013481:Superoxides; D013482:Superoxide Dismutase; D010269:Paraquat