| abstract |
Novel cyclic CRF agonist peptides have the amino acid sequence: (cyclo 30-33)Ac-Ser-Leu-Asp-Leu-Thr-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Glu-Ala-R32-R33-Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH2 wherein R32 is His, D-His or an equivalent alpha-amino acid; R33 is Lys or Orn. The N-terminus may be extended by Tyr, D-Tyr or Ile. 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-Ser7, D-Phe12, Nle21,38, Glu30, Lys33]r/hCRF(7-41); (cyclo 30-33)[Ac-Ser7, D-Phe12, Nle21,38, Glu30, D-His32, Lys33]r/hCRF(7-41); (bicyclo 20-23, 30-33)[Ac-Ser7, D-Phe12, Nle21,38, Lys23,33, Glu30, D-His32]-r/hCRF(7-41); (cyclo 30-33)[Ac-Ser7, D-Phe12, Nle18,21, Glu30, D-Ala32, Lys33]alpha-helicale CRF(7-41); and (cyclo 30-33)[Ac-Ser7, D-Phe12, Nle21,38, CML27,40, Glu30, Lys33]r/hCRF(7-41). Labelled agonist such as (cyclo 30-33)[Ac-I125Tyr6, D-Phe12, Nle21,38, Glu30, Lys33]r/hCRF(6-41) and (cyclo 30-33)[Ac-I125D-Tyr6, D-Phe12, Nle21,38, Glu30, D-His32, Lys33]r/hCRF(6-41) are useful in screening for more potent CRF agonists. |