Motlin-like polypeptide and use thereof

Details Motlin-like polypeptide and use thereof Motlin-like polypeptide and use thereof

1992-09-11

1995-07-11

Warden, Jill

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

15 to 23 amino acid residues in defined sequence

A61K 3800, C07K 1400

Patent

active

054322618

ABSTRACT:
A pharmaceutical composition for stimulating peristaltic contraction in the intestinal canal which contains a pharmaceutically acceptable carrier or excipient and an effective amount of a polypeptide, or a salt thereof, having a pharmacological activity similar to motilin. The polypeptide has the formula B.sub.1 -Z.sub.1 -A.sub.1 -Z.sub.2 -B.sub.2 -Thr-B.sub.3 -A.sub.2 -Glu-Z.sub.3 -C-Arg-X'-Gln-Glu-Lys-Glu-Arg-D-Lys-Gly-E-Y, with Z.sub.1,Z.sub.2 and Z.sub.3 each being an amino acid residue having a hydrophobic side-chain, A.sub.1 and A.sub.2 each being an amino acid residue such as Pro, Gly, Asn and Ser, B.sub.1, B.sub.2 and B.sub.3 are each an amino acid residue having a side-chain with an aromatic ring, C is Gln, Glu or Asp, D is Asn, Glu or Asp, X' is an amino acid residue other than Met, E is Gln, Lys or Arg, and Y is homoserine, homoserine-lactone or a peptide chain having amino acid residues not exceeding 10 and containing homoserine or homoserine-lactone at the C-terminal where the first amino acid of said peptide chain is other than Lys, Arg or Pro.

REFERENCES:
John C. Brown et al, Gastroenterology, vol. 62, No. 3, "Motilin, A Gastric Motor Activity-Stimulating Polypeptide: Final Purification, Amino Acid Composition, and C-Terminal Residues", pp. 401-404 (1972).
Schubert et al, Can J. Biochem., vol. 52, "Correction to the Amino Acid Sequence of Porcine Motilin", pp. 7-8 (1974).
U. Strunz et al, Comparison of Natural and Synthetic Motilin, "Gastroduodenal Motor Response to Natural Motilin and Synthetic Position 13-Substituted Motilin Analogues: A Comparative In Vitro Study", pp. 199-206.
Rose et al, 37 Advances in Protein Chemistry, pp. 1-2 (1985).
Brown et al, Gastroenterology, vol. 62, pp. 401-404 (1972).
Can. J. Biochem., vol. 52, pp. 7-10 (1974).
Gastroeneterology, vol. 80, pp. 456-460 (1981).
Scand. J. Gastroenterology, vol. 11, pp. 119-203 (1976).
Christofides, et al "Effect of Motilin on the Gastric Emptying of Glucose and Fat Humans", vol. 52 pp. 7-10 (1974).
Seino, et al, "Sequence of an Intestinal cDNA Encoding Human Motilin Precursor", vol. 223, 74-76, Feb., 1987.

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