Claims
- 1. A CRF peptide antagonist having the formula, or a nontoxic salt thereof: ##STR8## wherein R.sub.30 is Cys or Glu; R.sub.33 is Cys, Lys or Orn; provided that when R.sub.30 is Cys, R.sub.33 is Cys and when R.sub.30 is Glu, R.sub.33 is Lys or Orn, and provided further that the N-terminus may be extended by Asp-Leu-Thr, Leu-Thr or Thr.
- 2. The CRF peptide antagonist of claim 1 having the formula: ##STR9##
- 3. The CRF peptide antagonist of claim 1 having the formula: ##STR10##
- 4. The CRF peptide antagonist of claim 1 having the formula: ##STR11##
- 5. In a CRF peptide antagonist having the following formula, or a nontoxic salt thereof:
- (cyclo 30-33)D-Phe-His-Leu-Leu-Arg-Glu-R.sub.18 -Leu-R.sub.20 -Nle-R.sub.22 -R.sub.23 -Ala-R.sub.25 -Gln-Leu-Ala-R.sub.29 -R.sub.30 -Ala-R.sub.32 -R.sub.33 -Asn-Arg-R.sub.36 -Leu-Nle-R.sub.39 -R.sub.40 -R.sub.41 -NH.sub.2 wherein R.sub.18 is Val, Nle or Met; R.sub.20 is Glu or D-Glu; R.sub.22 is Ala or Thr; R.sub.23 is Arg or Lys; R.sub.25 is Asp or Glu; R.sub.29 is Gln or Glu; R.sub.32 is His or Ala; R.sub.36 is Lys or Leu; R.sub.39 is Glu or Asp; R.sub.40 is Ils or Glu; and R.sub.41 is Ile or Ala; with R.sub.20 being optionally be bonded to Lys.sup.23, wherein the improvement comprises R.sub.30 being either Glu or Cys and R.sub.33 being Lys, Orn or Cys; provided, however, that when R.sub.30 is Cys, R.sub.33 is Cys; and when R.sub.30 is Glu, R.sub.33 is Orn or Lys.
- 6. The peptide of claim 5 wherein R.sub.30 is Glu.
- 7. The peptide of claim 6 wherein R.sub.33 is Lys.
- 8. The peptide of claim 5 wherein R.sub.18 is Val, R.sub.23 is Arg, R.sub.32 is His, and R.sub.40 is Ile.
- 9. The peptide of claim 8 wherein R.sub.22 is Ala and R.sub.25 is Glu.
- 10. A CRF peptide antagonist having the formula, or a nontoxic salt thereof:
- (cyclo 30-33)R.sub.12 -His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-R.sub.30 -Ala-His-R.sub.33 -Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH.sub.2 wherein R.sub.12 is D-Phe or D-Tyr, R.sub.30 is Cys or Glu; R.sub.33 is Cys, Lys or Orn; provided that when R.sub.30 is Cys, R.sub.33 is Cys and when R.sub.30 is Glu, R.sub.33 is Lys or Orn, and provided further that the N-terminus may be extended by Asp-Leu-Thr, Leu-Thr or Thr.
- 11. The peptide of claim 10 wherein R.sub.33 is Lys.
- 12. In a CRF peptide antagonist having the following formula, or a nontoxic salt thereof:
- (cyclo 30-33)Y-D-Phe-His-Leu-Leu-Arg-Glu-Val-R.sub.19 -R.sub.20 -R.sub.21 -Ala-R.sub.23 -Ala-R.sub.25 -Gln-R.sub.27 -Ala-Gln-R.sub.30 -Ala-His-R.sub.33 -Asn-Arg-Lys-Leu-Nle-R.sub.39 -Ile-R.sub.41 -NH.sub.2 wherein Y is H, Ac, Fr, Acr, or Bz; R.sub.19 is Leu or CML; R.sub.20 is Glu or D-Glu; R.sub.21 is Nle or Met; R.sub.23 is Arg or Lys; R.sub.25 is Asp or Glu; R.sub.27 is Leu or CML; R.sub.39 is Glu or Asp; R.sub.41 is Ala or Ile; provided that the N-terminus may be extended by Asp-Leu-Thr, Leu-Thr or Thr, wherein the improvement comprises R.sub.30 being either Glu or Cys and R.sub.33 being Lys, Orn or Cys; provided, however, that when R.sub.30 is Cys, R.sub.33 is Cys; and when R.sub.30 is Glu, R.sub.33 is Orn or Lys.
- 13. The peptide of claim 12 wherein R.sub.23 is Arg and R.sub.25 is Glu.
- 14. The peptide of claim 12 wherein R.sub.39 is Glu, and R.sub.41 is Ile.
- 15. The peptide of claim 12 wherein R.sub.27 is CML.
- 16. The peptide of claim 15 wherein R.sub.19 is Leu.
Government Interests
This invention was made with Government support under grant number DK-26741 awarded by the National Institutes of Health. The Government has certain rights in this invention.
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Entry |
Life Sciences, vol. 51, pp. 189-193, 1992 (Hniby). |
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