title: Chemical modification of superoxide dismutase. Extension of plasma half life of the enzyme through its reversible binding to the circulating albumin.
abstract: Protection of organisms from oxidative stress is one of the major prerequisites for aerobic life. Since intravenously injected Cu++/Zn++-type superoxide dismutase (SOD) rapidly undergoes renal glomerular filtration and appears in urine in its intact form, its clinical use as a scavenger for superoxide radicals has been highly limited. To test whether reversible interaction of SOD with plasma albumin might decrease the rate of disappearance of the enzyme from the circulation, the lysyl residues of the human erythrocyte-type enzyme were covalently linked with poly-(styrene-co-maleic acid) butyl ester (SMA) via amide linkage. Affinity chromatographic analysis by an albumin-Sepharose column revealed that the enzyme samples labeled with SMA (SMA-SOD) tightly bound to the column, while unmodified SOD was eluted in the unbound fractions. SMA-SOD bound to the column could be eluted by the buffer solution containing 0.1% sodium dodecylsulfate. In vivo analysis revealed that intravenously administered SMA-SOD circulated bound to albumin with an extremely long half-life (6 h), while unmodified SOD rapidly underwent renal glomerular filtration with a plasma half-life of 4 min. Thus, SMA-SOD may effectively dismutase superoxide radicals in the circulation.
authors.affiliation: Department of Biochemistry, Kumamoto University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ogino
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Ando
authors.forename: M
authors.initials: M
authors.lastname: Awai
authors.forename: H
authors.initials: H
authors.lastname: Maeda
authors.forename: Y
authors.initials: Y
authors.lastname: Morino
mesh_terms: D000818:Animals; D002417:Cattle; D004795:Enzyme Stability; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D013482:Superoxide Dismutase