Rat hypothalamic GRF

Details Rat hypothalamic GRF Rat hypothalamic GRF

1983-04-26

1986-06-17

Phillips, Delbert R.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

530324, C07K 710, A61K 3743

Patent

active

045956766

ABSTRACT:
Rat hypothalamic GRF has been synthesized and has the formula: H-His-Ala-Asp-Ala-Ile-Phe-Thr-Ser-Ser-Tyr-Arg-Arg-Ile-Leu-Gly-Gln-Leu-Tyr- Ala-Arg-Lys-Leu-Leu-His-Glu-Ile-Met-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu -Gln-Arg-Ser-Arg-Phe-Asn-OH. The peptide is believed to be and is hereinafter referred to as rhGRF (for rat hypothalamic GH releasing factor). The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals and which have the formula: H-R.sub.1 -Ala-Asp-Ala-Ile-Phe-Thr-R.sub.8 -Ser-R.sub.10 -Arg-R.sub.12 -R.sub.13 -Leu-R.sub.15 -Gln-Leu-R.sub.18 -Ala-Arg-Lys-Leu-Leu-R.sub.24 -R.sub.25 -Ile-R.sub.27 -R.sub.28 -Arg-Gln-Gln-Gly-Glu-R.sub.34 -Asn-Gln-Glu-R.sub.38 -R.sub.39 -R.sub.40 -Arg-R.sub.42 -R.sub.43 -R.sub.44 -Y wherein R.sub.1 is Tyr, Met, D-Tyr, Leu, D-His or His; R.sub.8 is Ser or Asn; R.sub.10 is Tyr or D-Tyr; R.sub.12 is Arg or Lys; R.sub.13 is Ile or Val; R.sub.15 is Gly or D-Ala; R.sub.18 is Tyr or Ser; R.sub.24 is His or Gln; R.sub.25 is Glu or Asp; R.sub.27 is Met, Ala, Nle, Ile, Leu or Val; R.sub.28 is Asn or Ser; R.sub.34 is Arg or Ser; R.sub.38 is Gln or Arg; R.sub.39 is Arg or Gly; R.sub.40 is Ser or Ala; R.sub.42 is Phe or Ala; R.sub.43 is Asn or Arg; R.sub.44 is a natural amino acid or des-R.sub.44 ; and Y signifies the carboxyl moiety of the amino acid residue at the C-terminus and is the radical --COOR,--CRO,--CONHNHR,--CON(R)(R') or --CH.sub.2 OR, with R and R' being lower alkyl, fluoro lower alkyl or hydrogen.
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 to animals, including humans, to stimulate the release of GH and may be used diagnostically.

REFERENCES:
"Growth Hormone-Releasing Factor from a Human Pancreatic Tumor that Caused Acromegaly", Science, vol. 218, pp. 585-587, Nov. 1982, Guillemin et al.
"Characterization of a Growth Hormone-Releasing Factor from a Human Pancreatic Islet Tumour", Nature, vol. 300, pp. 276-278, 11/82, Rivier et al.
Spiess et al., Biochemistry, 21, 6037-6040, (1982).
Spiess et al., Nature, 303(9), 532-535, (1983).
Thorner et al., The Lancet, I, No. 8314/5, 24-28, (1983).
Esch et al., The Journal of Biological Chemistry, 258, No. 3, 1806-1812, (Feb. 10, 1983).
Guillemin, Science, 218, 585-587, (1982).
Parsons, Peptide Hormones, University Park Press, Baltimore, Ch. 1, p. 6.
Krulich et al., Endocrinology, 88, 783-790 (1968).
Krulich et al., Endocrinology, 88, 783-790 (1968).

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