The Salk Institute for Biological Studies

Peter Bohlen

Nicholas C Ling

Frederick S Esch

Andrew J Baird

Denis Gospodarowicz

Roger C Guillemin

Paul E Brazeau, Jr

Fred S Esch

William B Wehrenberg

Paul E Brazeau

Substantially pure mammalian basic fibroblast growth factors are produced. The amino acid residue sequences of bovine and human bFGF are disclosed as well as a DNA chain encoding the polypeptide of the bovine species. By appropriately inserting a synthesized DNA chain into a cloning vector and using the cloning vector to transform cells, synthetic bovin bFGF can be obtained from transformed cell lines, both prokaryotic and eukaryotic.

Bovine basic fibroblast growth factor

Substantially pure mammalian basic fibroblast growth factors are produced. The amino acid residue sequences of bovine and human bFGF are disclosed as well as a DNA chain encoding the polypeptide of the bovine species. By appropriately inserting a synthesized DNA chain into a cloning vector and using the cloning vector to transform cells, synthetic bFGF can be obtained from transformed cell lines, both prokaryotic and eukaryotic.

Basic fibroblast growth factor

Substantially pure bovine pituitary fibroblast growth factor, a 146 amino acid residue polypeptide, is produced. The amino acid residue sequence of bpFGF is disclosed as well as a DNA chain encoding the polypeptide. By appropriately inserting a synthesized DNA chain into a cloning vector and using the cloning vector to transform cells, synthetic bpFGF can be obtained from transformed cell lines, both prokaryotic and eukaryotic.

Bovine fibroblast growth factor

Basic Fibroblast Growth Factor (FGF) is substantially purified by the employment of affinity chromatography using heparin-linked support material. Described is a simplified three step procedure for extracting basic FGF from either mammalian brain or mammalian pituitary tissue. Salt precipitation, e.g., with ammonium sulfate is used to provide a partially purified precipitate that is then subjected to ion-exchange chromatography, e.g., using a Carboxymethyl-Sephadex column. Substantially pure basic FGF fractions are then obtained by fractionating the further partially purified fractions using affinity chromatography on a heparin-linked support e.g., Heparin-Sepharose.

Isolation of fibroblast growth factor

The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in mammals and which have the formula: H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser- Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu -Gln-Gly-Ala-Arg-Val-Arg-Leu-Y wherein Y is OH or NH.sub.2. These peptides or biologically active fragments thereof, or analogs thereof having well-known substitutions and, or additions, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to mammals, including humans, and may be used diagnostically. The peptides are useful in stimulating the release of GH and accelerating growth in warm-blooded non-human animals, particularly pigs, and in improving aquiculture.

Porcine GRF

A synthetic peptide is extremely potent in stimulating the release of pituitary GH in mammals, particularly in sheep, since it is the replicate of the native (hormone) releasing factor of the sheep hypothalamus. It contains the following sequence: Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Ile-Leu-Gly-Gln-Leu-Ser-Al a-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu-G ln-Gly-Ala-Lys-Val-Arg-Leu. This peptide or a biologically active fragment thereof, or analogs thereof having well-known substitutions and/or additions, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to mammals and may be used diagnostically. The peptide is particularly useful in stimulating the release of GH so as to accelerate growth in warm-blooded non-human animals, particularly sheep, and/or to improve aquiculture.

Ovine GRF

The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in mammals and which have the formula: H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser- Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu -Gln-Gly-Ala-Lys-Val-Arg-Leu-Y wherein Y is OH or NH.sub.2. These peptides or biologically active fragments thereof, or analogs thereof having well-known substitutions and/or additions, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to mammals, including humans, and may be used diagnostically. The peptides are useful in stimulating the release of GH so as to accelerate growth in warm-blooded non-human animals, particularly cattle, and/or to increase the production of milk in lactating cows, and also in improving aquiculture.

Bovine GRF

PGRF has been synthesized. The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in mammals and which have the formula: ##STR1## wherein R is OH or NH.sub.2, R.sub.34 is Ser or Ala, R.sub.38 is Arg or Ser, R.sub.40 is Ala or Arg and R.sub.41 is Arg, Arg-Ala, Arg-Ala-Arg, Arg-Ala-Arg-Leu or des-R.sub.41. These peptides or biologically active fragments thereof, or analogs thereof having well-known substitutions and/or additions, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to mammals, including humans, and may be used diagnostically.

Mammalian PGRF

28-member residue and 25-member residue peptides have been synthesized containing the tetradecapeptide somatostatin that are more potent than somatostatin. Somatostatin-28 has the formula: ##STR1## The three N-terminal amino acid residues are absent in somatostatin-25. Somatostatin-28 or somatostatin-25 or a pharmaceutically acceptable addition salt thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals in the same manner as somatostatin.

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Uster, Switzerland

Peter Bohlen