Chimeric fibroblast growth factors

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Hormones – e.g. – prolactin – thymosin – growth factors – etc.

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435 691, C07K 1300

Patent

active

053027027

ABSTRACT:
The present invention relates to novel chimeric fibroblast growth factors (FGF) wherein the alanine at amino acid 3 and serine 5 of native human recombinant basic fibroblast growth factor are replaced with glutamic acid. The N-terminus sequence of the present chimeric FGFs identify homology with that of human acidic fibroblast growth factor. The mitogenic properties of the native human recombinant basic FGF are exhibited by the present chimeric FGFs, and they are efficiently expressed in E. coli at significantly greater yields that previously reported. Novel variants of this new glu.sup.3,5 basic fibroblast growth factor, such as those in which cysteine 78 and cysteine 96 are replaced, e.g., with serine or other amino acids, to produce stabilized versions of the glu.sup.3,5 basic FGF and eliminate disulfide scrambled forms, are also described.

REFERENCES:
patent: 4518584 (1985-05-01), Mark et al.
patent: 4588585 (1986-05-01), Mark et al.
patent: 4959314 (1990-09-01), Mark et al.
Daniel M. Bollag et al., Preliminary X-Ray Crystallographic Analysis of a Modified Basic Fibroblast Growth Factor, J. Mod. Biol. 218:493-494 (1991).
Seno et al. Biochem and Biophys Res. Comm 151(2): 701-708 (1988).

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