| 摘要 |
<p>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 α-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-Ser?7, D-Phe12, Nle21,38, Glu30, Lys33¿]r/hCRF(7-41); (cyclo 30-33)[Ac-Ser?7, D-Phe12, Nle21,38, Glu30, D-His32, Lys33¿]r/hCRF(7-41); (bicyclo 20-23, 30-33)[Ac-Ser?7, D-Phe12, Nle21,38, Lys23,33, Glu30, D-His32¿]-r/hCRF(7-41); (cyclo 30-33)[Ac-Ser?7, D-Phe12, Nle18,21, Glu30, D-Ala32, Lys33¿]α-helicale CRF(7-41); and (cyclo 30-33)[Ac-Ser?7, D-Phe12, Nle21,38, CML27,40, Glu30, Lys33¿]r/hCRF(7-41). Labelled agonist such as (cyclo 30-33)[Ac-I?125Tyr6, D-Phe12, Nle21,38, Glu30, Lys33¿]r/hCRF(6-41) and (cyclo 30-33)[Ac-I?125D-Tyr6, D-Phe12, Nle21,38, Glu30, D-His32, Lys33¿]r/hCRF(6-41) are useful in screening for more potent CRF agonists.</p> |
