Cyclic CRF agonists

Details Cyclic CRF agonists Cyclic CRF agonists

1997-05-30

1998-10-20

Tsang, Cecilia J.

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

Corticotropin ; related peptides

530317, 514 2, 514 9, 930 21, 930 70, 930260, C07K 16695, C07K 764, A61K 3812

Patent

active

058247718

ABSTRACT:
Novel cyclic CRF agonist peptides have the amino acid sequence: (cyclo 30-33)Ac-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu -Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-R.sub.30 -Ala-R.sub.32 -R.sub.33 -Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH.sub.2 wherein R.sub.30 is Glu or Cys; R.sub.32 is His, D-His or an equivalent .alpha.-amino acid; R.sub.33 is Lys, Orn or Cys. The N-terminus may be extended by Ser-Glu-Glu or shortened by up to three more residues. Lys may be substituted for Arg.sup.23, and its side chain connected by a lactam bridge to Glu.sup.20 to form a bicyclic peptide. Certain disclosed CRF agonists include: D-His.sup.32, Lys.sup.33 !r/hCRF(4-41), Lys.sup.33 !r/hCRF(7-41), D-His.sup.32, Lys.sup.33 !r/hCRF(7-41), Lys.sup.23,33, Glu.sup.30, D-His.sup.32 !-r/hCRF(4-41), D-Ala.sup.32, Lys.sup.33 !.alpha.-helical CRF(7-41), and Glu.sup.30, Lys.sup.33 !r/hCRF(7-41). Nle.sup.21,38, Glu.sup.30, D-His.sup.32, Lys.sup.33 !r/hCRF and (cyclo D-His.sup.32, Lys.sup.33 !r/hCRF(3-41) are useful in screening for more potent CRF agonists.

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