4sod
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RATIONAL DESIGN AND EXPRESSION OF A HEPARIN-TARGETED HUMAN SUPEROXIDE DISMUTASE
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Structural highlights
Publication Abstract from PubMedIn order to improve the therapeutic effectiveness of human Cu,Zn superoxide dismutase (HSOD) by targeting it to cell surfaces and increasing its circulatory half-life, we have designed and expressed a heparin-binding derivative of HSOD. This design was based on the idea that structurally independent protein units, HSOD and the heparin-binding A+ helix from protein C inhibitor, could be combined with a carefully chosen linker, GlyProGly, to form a stable, bifunctional protein. The chimeric HSOD-GlyProGly-A+ protein was expressed and secreted to the periplasm of E. coli and had normal SOD activity. HSOD-GlyProGly-A+ had a significantly increased retention time relative to wild-type HSOD on a heparin affinity column, indicating that it was successfully targeted to heparin, and this binding was maintained at physiological ionic strength. When administered to mice, HSOD-GlyProGly-A+ had a half-life of approximately 15 minutes, twice that of wild-type HSOD. Our rational design approach should be generally applicable to the creation of bifunctional chimeric molecules. Rational design and expression of a heparin-targeted human superoxide dismutase.,Boissinot M, Kuhn LA, Lee P, Fisher CL, Wang Y, Hallewell RA, Tainer JA Biochem Biophys Res Commun. 1993 Jan 15;190(1):250-6. PMID:8422249[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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