rCRF and analogs

Details rCRF and analogs rCRF and analogs

1983-04-14

1984-12-18

Phillips, Delbert R.

Chemistry: analytical and immunological testing

Peptide, protein or amino acid

424 2, 424177, 2601125R, G01N 100, A61K 3700, C07C10352

Patent

active

044891636

ABSTRACT:
rCRF (rat Corticotropin Releasing Factor) has been isolated, characterized and found to have the formula: H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val- Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu -Met-Glu-Ile-Ile-NH.sub.2. Analogs are disclosed that are at least as potent as rCRF, and rCRF or these analogs orpharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to animals, including humans, to achieve a substantial elevation of ACTH, .beta.-endorphin, .beta.-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels and/or a lowering of blood pressure over an extended period of time. They may also be used as stimulants to elevate mood and improve memory and learning, as well as diagnostically.
In the analogs, one or more of the first three N-terminal residues may be deleted or may be substituted by a peptide up to 10 amino acids long and/or by an acylating agent containing up to 7 carbon atoms. A number of other substitutions may also be made throughout the chain.

REFERENCES:
Bristow, et al., J. of Endocrinology (1980), 84, 189-197.
Science, Sep. 18, 1981, Vale et al., pp. 1394-1394, "Characterization of a 41-Residue Ovine Hypothalamic Peptide that Stimulates Secretion of Corticotropin and .beta.-Endorphin".
Peptides, vol. 3, pp. 859-867 (1982), Ichikawa, et al., "Isolation and Amino Acid Sequence of Urotensin I, a Vasoactive and ACTH-Releasing Neuropeptide, from the Carp (Cyprinus Carpio) Urophysis".

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