发明名称 |
CRF ANALOG CONJUGATES |
摘要 |
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.
|
申请公布号 |
CA1335227(C) |
申请公布日期 |
1995.04.11 |
申请号 |
CA19880569986 |
申请日期 |
1988.06.21 |
申请人 |
SALK INSTITUTE FOR BIOLOGICAL STUDIES (THE);SALK INSTITUTE FOR BIOLOGICAL STUDIES (THE) |
发明人 |
VALE, WYLIE W., JR.;VALE, WYLIE W., JR.;RIVIER, JEAN E. F.;RIVIER, JEAN E. F.;SCHWARTZ, JEFFREY;SCHWARTZ, JEFFREY |
分类号 |
C07K14/575;(IPC1-7):C07K7/38;A61K47/48 |
主分类号 |
C07K14/575 |
代理机构 |
|
代理人 |
|
主权项 |
|
地址 |
|