Crf analog conjugates

Details Crf analog conjugates Crf analog conjugates

C - Chemistry, Metallurgy

07

K

167/129, 530/7.3

C07K 14/575 (2006.01) A61K 47/48 (2006.01)

Patent

CA 1335227

Agonists and antagonists of rCRF are disclosed that exhibit good binding affinity to CRF receptors. One exemplary agonist is: H-Ser-Gln-Glu-Pro-Pro-Ile-Ser- Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Met-Leu-Glu-Met- Ala-Arg-Ala-Glu-Gln-Glu-Ala-Glu-Gln-Ala-Ala-Leu-Asn-Arg- Leu-Leu-Leu-Glu-Glu-Ala-NH2. In the agonists, one or more of the first five N-terminal residues may be deleted or may be substituted by a peptide up to 10 amino acids long. A number of other substitutions may also be made throughout the chain. Similar peptides which function as CRF antagonists are created by deleting the first 7, 8 or 9 N-terminal residues. These analogs are coupled to a cytotoxin, such as gelonin, by a dialdehyde or the like, e.g., glutaraldehyde. The conjugates may be used to eliminate CRF Target Cells, and thus to regulate secretion of ACTH, .beta.-lipotropin and the like. Such conjugates can also be administered to alleviate conditions associated with hyperactivity of the hypothalamus-pituitary adrenal axis as well as neoplastic diseases associated with tumors that express CRF receptor.

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