Cyclic CRF analogs

Details Cyclic CRF analogs Cyclic CRF analogs

1994-12-12

1997-09-02

Chan, Christina Y.

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

Corticotropin ; related peptides

530317, 930 21, 930 70, 930260, C07K 14695, C07K 764

Patent

active

056632924

ABSTRACT:
Improved CRF antagonist peptides have the formula: ##STR1## 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. The N-terminus may be extended by Asp-Leu-Thr. Lys may be substituted for Arg.sup.23 and its side chain connected by a lactam bridge to Glu.sup.20 to form a dicyclic peptide. Specific CRF antagonists disclosed include (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Glu.sup.30, Lys.sup.33 ]rCRF(12-41); (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Glu.sup.30, Orn.sup.33 ]rCRF(12-41), (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Cys.sup.30,33 ]rCRF (12-41) and (bicyclo 20-23,30-33) [D-Phe.sup.12, Nle.sup.21,38, Lys.sup.23,33, Glu.sup.30 ]-rCRF(12-41).

REFERENCES:
patent: 4632780 (1986-12-01), Seidah et al.
patent: 5064939 (1991-11-01), Rivier et al.
patent: 5109111 (1992-04-01), Rivier et al.
patent: 5245009 (1993-09-01), Kornreich et al.
patent: 5278146 (1994-01-01), Rivier et al.
Life Sciences, vol. 51, pp. 189-193, 1992 (Hniby).
Biopolymers, vol. 31, pp. 745-750, 1991 (Gilon).

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