Melanin-concentrating hormones

Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 15 to 23 amino acid residues in defined sequence

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536 27, 530827, 530854, 435 694, 4353201, C07K 764, C12N 1516

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active

050496557

ABSTRACT:
Mammalian melanin-concentrating hormone (MCH) is isolated from rat tissue, purified and characterized. These MCH peptides are useful for treating skin disorders, for suppressing the proliferation of skin tumor cells, such as melanomas in mammals, and for modulating the secretion of ACTH. Generally, peptides are provided which have the following formula: ##STR1## or which are naturally occurring homologs of the peptide with said formula. The peptides which are the naturally occurring MCH homologs of mammalian species other than rat can also be obtained using the materials disclosed, as demonstrated specifically with human MCH, which is found to have the same structure as rat MCH. Also disclosed are the amino acid sequences of, and the nucleotide sequences of the cDNAs which encode, the putative precursors of rat MCH and human MCH. These precursors may also include one or more biologically active peptides N-terminally of the mature MCH's. Among these peptides, which are thought to be formed from the MCH precursors, are the peptide with the sequence H-Glu-Ile-Gly-Asp-Glu-Glu-Asn-Ser-Ala-Lys-Phe-Pro-Ile-NH.sub.2, which is cross-reactive with antibodies against alpha-MSH and CRF, and the peptide with the sequence H-Gly-X.sub.NGE -Phe-Pro-Ala-Glu-Asn-Gly-Val-Gln-Asn-Thr-Glu-Ser-Thr-Gln-Glu-OH, wherein X.sub.NGE is Pro-Ala-Val or Ser-Val-Ala, which is cross-reactive with antibodies against GRF.

REFERENCES:
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Zamir et al., "Melanin-Concentrating Hormone: Unique Peptide Neuronal System in the Rat Brain and Pituitary Gland", Proc. Natl. Acad. Sci. U.S.A. 83, pp. 1528-1531, 3/86.
Kawauchi et al., "Characterization of Melanin-Concentrating Hormone in Chum Salmon Pituitaries", Nature, vol. 305 pp. 321-323 (9/22/83).
White et al., Principles of Biochemistry Sixth Ed. p. 829 (1978).
Scopes, Protein Purification Second Ed. pp. 167-172 (1987).
Wilkes, et al., "Synthesis and Biological Actions of Melanin Concentrating Hormone", Biochemical and Biophysical Research Communications 122, 316 (1984).
Baker, et al., "Further Observations on the Distribution and Properties of Teleost Melanin Concentrating Hormone", General and Comparative Endocrinology 50, 423 (1983).
Naito, et al., "Melanin-Concentrating Hormone-Like Immunoreactive Material in the Rat Hypothalamus; Characterization and Subcellular Localization", Cell and Tissue Research 253, 291 (1988).
Sekiya, et al., "The Distribution of Melanin-Concentrating Hormone-Like Immunoreactivity in the Central Nervous System of Rat, Guinea-Pig, Pig and Man", Neuroscience 25 925 (1988).
Alex N. Eberle, "The Melanotropins", Chapters 15, 16, and 20, Karger Publishing Company (1988).

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