Synthesis and characterization of superoxide dismutase-deferoxamine conjugate via polyoxyethylene: a new molecular device for removal of a variety of reactive oxygen species.
A conjugate of Cu,Zn-superoxide dismutase (SOD) with a strong iron chelating agent, deferoxamine (DFO), was synthesized (SOD-POE-DFO) via polyoxyethylene (POE) as a linking agent. N-terminal amino groups of lysine residues in SOD are modified with 1:1 binding products of polyoxyethylene and deferoxamine (POE-DFO) through a covalent amido bond. The mean number of the POE-DFO bound per one SOD molecule is calculated to be 3.3 by determining the C/N ratio after elemental analysis. The half-life of the SOD-POE-DFO is about 1.2 h in rats, whereas that of free SOD is about 5-10 min. POE plays the part not only of the linking agent but also of expanding the lifetime in the circulation. The SOD-POE-DFO possesses both the metal chelating ability (for DFO) and the ability of scavenging superoxide radicals (for SOD). Therefore, the SOD-POE-DFO of the present study can eliminate the superoxide radical and free iron simultaneously and in the same location, and thus, it would be a molecular device with multiple functions which prevents the damage to tissues by scavenging the variety of reactive oxygen species.
Sato
H
H
Central Research Laboratories, Ajinomoto Company, Inc, Kawasaki, Japan.
Watanabe
M
M
Iwashita
Y
Y
D000818:Animals; D002614:Chelating Agents; D003676:Deferoxamine / Q000737:chemistry* / Q000493:pharmacokinetics; D016166:Free Radical Scavengers; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics
D002614:Chelating Agents; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; D003676:Deferoxamine