| 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-R30-Ala-R32-R33-Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH2 wherein R30 is Glu or Cys; R32 is His or a D-amino acid such as D-His, D-Arg or similar; R33 is Lys, Orn or Cys. The N-terminus may be extended by Ser-Glu-Glu. Lys may be substituted for Arg23, and its side chain connected by a lactam bridge to Glu20 to form a bicyclic peptide. Certain disclosed CRF agonists include: (cyclo 30-33)[Ac-Pro4, D-Phe12, Nle21,38, D-His32, Glu30, Lys33]r/hCRF(4-41), (cyclo 30-33)[Ac-Pro4, D-Phe12, Nle21,38, D-His32, Glu30, Orn33]r/hCRF(4-41), (cyclo 30-33)[Ac-Pro4, D-Phe12, Nle21,38, Cys30,33, D-His32]r/hCRF(4-41), (bicyclo 20-23,30-33)[Ac-Pro4, D-Phe12, Nle21,38, Lys23,33, Glu30, D-His32]-r/hCRF(4-41), (cyclo 30-33)[Ac-Pro4, D-Phe12, Nle21,38, CML27, Glu30, imBzlD-His32, Lys33]r/hCRF(4-41) and (cyclo 30-33)[Ac-Pro4, D-Phe12, Nle21,38, Glu30, D-Arg32, Lys33]r/hCRF(4-41). Labelled agonists such as (cyclo 30-33)[I125Tyro, D-Phe12, Nle21,38, Glu30, D-His32, Lys33]r/hCRF and (cyclo 30-33)[I125D-Tyr3, D-Phe12, Nle21,38, Glu30, D-His32, Lys33]r/hCRF(3-41) are useful in screening for more potent agonists. |