Ab Kabi

Hans Uno Sievertsson

Knut Oivind Uthne

Ronny Hugo Lundin

Linda Fryklund

Gertrud Elisabeth Sjodahl

Novel synthetic peptides of the general formula ##STR1## and the corresponding reduced, linear form. The cyclic form of the peptide is produced by oxidation of the corresponding linear compound thereby providing the divalent dithio group --S--S-- joining the beta carbon of each of the cysteine moieties. In the above formula X is serine (SER) or lysine (Lys), and Y is OH or Thr-Glu-Gly-Phe. The obtained synthetic peptides, in either form, are useful in promoting growth of cells of mammalian tissues.

Synthetic peptides having growth promoting activity

The application discloses (A) a growth-promoting polypeptide having molecular weight from about 5,000 to about 7,000 chromatographic mobility under electrophoresis from about 0.25 to about 0.37 relative to lysine at pH 5 and from about 0.17 to about 0.43 relative to aspartic acid at pH 7.5, terminal amino acid at its amino end being asparagine or aspartic acid, and respective amounts of aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, leucine, tyrosine, phenylalanine, lysine, arginine, trypophan, and cysteine or carboxymethyl cysteine, and also a couple of instances also methionine, isoleucine and histidine; and (B) the derivation of the polypeptides from blood serum or plasma or a plasma fraction by combined steps of (a) homogenizing the starting material in water, (b) admixing a solution of hydrochloric acid in ethanol thereby splitting the polypeptide from its carrier proteins and precipitating them, (c) adjusting the pH to 8.4 to provide a precipitate, (d) separating it, (e) adjusting the pH of the liquid residue to 3, (f) admixing a water-insoluble strongly acidic cation exchange matrix of sulfopropyl-oxygen-linked-substitued dextran cross-linked with epichlorhydrin at pH 3, (g) separating the gel matrix from the liquid, (h) eluting the polypeptide-containing material from the matrix with (x) ammonium acetate at pH 10 or (y) 0.75M ammonium bicarbonate; and (i) precipitating the polypeptide by admixing acetone.

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Sollentuna, Sweden

Hans Uno Sievertsson