Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1985-08-29
1987-08-25
Phillips, Delbert R.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
530324, A61K 3743, C07K 710
Patent
active
046893180
ABSTRACT:
Human pancreatic GRF and the hypothalamic GRFs for the human and several other mammalian species were earlier characterized and synthesized. The invention provides synthetic peptides which are potent stimulators of the release of pituitary GH in animals, including humans, and which have the formula: R.sub.1 -R.sub.2 R.sub.3 -Ala-R.sub.5 -R.sub.6 -R.sub.7 -R.sub.8 -R.sub.9 -R.sub.10 -R.sub.11 -R.sub.12 -R.sub.13 -Leu-R.sub.15 -Gln-Leu-R.sub.18 -R.sub.19 -R.sub.20 -R.sub.21 -Leu-Leu-Gln-Glu-R.sub.26 -R.sub.27 -R.sub.28 -Arg-Y wherein R.sub.1 is Tyr, D-Tyr, Met, Phe, D-Phe, Leu, His or D-His, which has either a C.sup.a Me or N.sup.a Me substitution or is unsubstituted; R.sub.2 is Ala or D-Ala; R.sub.3 is Asp or D-Asp; R.sub.5 is Ile or Leu; R.sub.6 is Phe or Tyr; R.sub.7 is Ser or Thr; R.sub.8 is Ser, Asn, Thr or Gln; R.sub.9 is Ala or Ser; R.sub.10 is Tyr, Phe or Leu; R.sub.11 in Arg, Orn or Lys; R.sub.12 is Arg, Orn or Lys; R.sub.13 is Ile, Leu, Phe or Val; R.sub. 15 is Gly or Ala; R.sub.18 is Ala or Ser; R.sub.19 is Ser or Ala; R.sub.20 is Arg, Orn or Lys; R.sub.21 is Arg, Orn or Lys; R.sub.26 is Leu, Ile, Val or Phe; R.sub.27 is Nle, Nva or a natural amino acid; R.sub.28 is Ala, Leu, Asn, Gln, or Ser; and Y is OH or NH.sub.2 ; provided however that at least four of the residues constituting R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.15, R.sub.18, R.sub.19, R.sub.20, R.sub.21 and R.sub.26 are different from the residues appearing in that respective position in the native molecule. These peptides as well as nontoxic salts thereof may be administered to animals, including humans and cold-booded animals, to stimulate the release of GH and may be used diagnostically.
REFERENCES:
patent: 4514331 (1985-04-01), Kaiser
patent: 4518586 (1985-05-01), Rivier et al.
patent: 4528190 (1985-07-01), Vale, Jr. et al.
patent: 4529595 (1985-07-01), Rivier et al.
patent: 4595676 (1986-06-01), Spiess et al.
E. T. Kaiser and F. J. Kezdy, Science, vol. 223, pp. 249-225, 1/20/84 "Amphiphilic Secondary Structure: Design of Peptide Hormones".
Kaiser Emil T.
Velicelebi Gonul
Phillips Delbert R.
The Salk Institute for Biological Studies
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