GRF Analogs

Details GRF Analogs GRF Analogs

1983-01-13

1985-07-16

Phillips, Delbert R.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

2601125R, C07C10352, A61K 3702

Patent

active

045295956

ABSTRACT:
Human pancreatic GRF analogs which are extremely potent in stimulating the release of pituitary GH in mammals and which have the formula: H-R-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-R.sub.15 -Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R.sub.27 -Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Y wherein R is selected from the D- and L-isomers of Tyr, Phe and His, R.sub.15 is Gly or D-Ala, R.sub.27 is selected from the group consisting of the D- and L-isomers of Ala, Nle, Ile, Leu, Met and Val, and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical --COOR.sub.1,--CR.sub.1 O,--CONHNHR.sub.1,--CON(R.sub.1)(R.sub.2) or --CH.sub.2 OR.sub.1, with R.sub.1 and R.sub.2 being lower alkyl or hydrogen, provided that when R is Tyr, R.sub.27 is other than Met. Phe may be substituted for Tyr in the 10-position, and D-Ala may be substituted for Gly in the 28-position. These peptides or biologically active fragments thereof, which will generally extend from the N-terminal to the vicinity of a residue between positions 27 and 32, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to animals, including humans, and may be used diagnostically.

REFERENCES:
Esch et al., Biochemical and Biophysical Research Communications, 109, No. 1, 152-158, (1982).
Esch et al., The Journal of Biological Chemistry, 258, No. 3, 1806-1812, (1983).
J. Spiess et al., Biochemistry, 21, 6037-6040, (1982).
Thorner et al., The Lancet, Jan. 1/8, 24-28, (1983).
Vance et al., Journal of Clinical Endocrinology and Metabolism, vol. 58, No. 5, 1984, pp. 838-844.
Borges et al., Journal of Clinical Endocrinology and Metabolism, vol. 59, No. 1, 1984, pp. 1-6.
Scanes et al., Life Sciences, vol. 34, 1984, pp. 1127-1133.
Science, vol. 218, Nov. 5, 1982, Guillemin et al., "Growth Hormone-Releasing Factor from a Human Pancreatic Tumor That Caused Acromegaly".

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