Polypeptide analogs of human manganese superoxide dismutase and

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Oxidoreductase

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424 944, C12N 902, A61K 3750

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active

052468470

ABSTRACT:
A double-stranded cDNA molecule which includes DNA encoding human manganese superoxide dismutase has been created. The sequence of one strand of a double-stranded DNA molecule which encodes human maganese superoxide dismutase has been discovered. Such molecules may be introduced in procaryotic, e.g., bacterial, or eukaryotic, e.g., yeast or mammalian, cells and the resulting cells cultured or grown under suitable conditions so as to produce human manganese superoxide dismutase or analogs thereof which may then be recovered. Human MnSOD or analogs thereof may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs, or treat inflammations.
The invention also concerns a method of producing enzymatically active human manganese superoxide dismutase or an analog thereof in a bacterial cell which contains and is capable of expressing a DNA sequence encoding the superoxide dismutase by maintaining the bacterial cell under suitable conditions and in a suitable production medium. The production medium is supplemented with an amount of Mn.sup.++ so that the concentration of Mn.sup.++ in the medium is greater than about 2 ppm.
This invention also concerns a method of recovering purified enzymatically active manganese superoxide dismutase from bacterial cells.

REFERENCES:
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Freifelder, D., Molecular Biology (Jones & Bartlett Publishers, Boston, MA) pp. 826-833 (1983).
Stryer, L., Biochemistry, W. H. Freeman and Co., San Francisco p. 18 (1975).
Coombs, J., Dictionary of Biotechnology, Elsevier, New York p. 248 (1986).
Steinman, H. M., Superoxide Dismutase (Oberly, ed.), CRC Press, Florida pp. 11-68.
Barra, D. et al., FEBS Letters 120: 53-56 (1980).
Joe M. McCord and Irwin Fridovich, Superoxide Dismutase, J. Biol. Chem. 224(22): 6049-6055 (1969).
Stryer, L., Biochemistry, W. H. Freeman and Co., San Francisco, CA p. 30 (1975).
Barra et al. J. Biol. Chem. 259: 12595-12601, 1984.

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