rCRF and analogs

• Main Authors: RIVIER, JEAN E. F, VALE, WYLIE W., JR, SPIESS, JOACHIM
• Format: Patent
• Language: English; French; German
• Published: 03.11.1993
• Edition: 5
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

Rat Corticotropin Releasing Factor (rCRF) and the human counterpart thereof 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-NH2. Analogs are disclosed that are at least as potent. One which has been found to be particularly potent is: H-Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr- Phe-His-Leu-Leu-Arg-Glu-Met-Leu-Glu-Met- Ala-Lys-Ala-Glu-Gln-Glu-Ala-Glu-Gln-Ala- Ala-Leu-Asn-Arg-Leu-Leu-Leu-Glu-Glu-Ala-NH2. These analogs or pharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to mammals, 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.