DNA encoding glycosylated FGF and production thereof

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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4353201, 435 691, 435 694, 4352523, 4352551, 43525233, 536 2351, 530399, C07H 2100, C07K 1450, C12N 1518, C12N 1563

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054649439

ABSTRACT:
Disclosed are (1) a mutein of a fibroblast growth factor (FGF), the DNA having introduced therein at least one nucleotide sequence coding for a glycosylation site, (2) a DNA coding for the mutein of (1), (3) a vector containing the DNA of (2), (4) a transformant transformed with the vector of (3), and (5) a process for producing the mutein which comprises cultivating in a culture medium the transformant of a yeast or animal cell transformed with a vector of (3), and producing and accumulating the mutein of (1) in the culture medium, whereby the FGF mutein into which at least one glycosylation site has been introduced is improved in productivity, stability and activities, and advantageously used as medicine.

REFERENCES:
Jambarini et al J. Biol. Chem. 257(16):9692-97 (1982).
Abraham et al Science 233:545-548 (1986).
B. Hofer et al., Bio Chem. Hoppe-Seyler, "Modification and Introduction of Protein Glyxcosylation Sites by Site Specific Mutagenesis: Studies on Human Interleukin 2", 368:9, p. 1060 (1987).
G. Gimenez-Gallego et al., Biochemical & Biophysical Research Communications, "The Complete Amino Acid Sequence of Human Brain-Derived Acidic Fibroblast Growth Factor", 138:2, pp. 611-617, (1986).
H. Senoo et al., Biochemical & Biophysical Research Communications, "Stabilizing Basic Fibroblast Growth Using Protein Engineerig", 151:2, pp. 701-708, (1988).
G. Fox et al., The Journal of Biological Chemistry, "Production, Biological Activity, and Structure of Recombinant Basic Fibroblast Growth Factor and an Analog with Cysteine Replaced by Serine", 263, pp. 18452-18458, (1988).
T. Kurokawa et al., FEBS Letters, "Cloning and Expression of cDNA Encoding Human Basic Fibroblast Growth Factor", 213, pp. 189-194, (1987).

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