New class of corticotropin-releasing factor (CRF) antagonists: small peptides having high binding affinity for CRF receptor

J Med Chem. 2004 Feb 26;47(5):1075-8. doi: 10.1021/jm034180+.


The discovery of small and potent peptide antagonists of the corticotropin-releasing factor (CRF) receptor is described. Through the structure-activity relationship studies of 12-amino acid peptide corresponding to the C-terminal residues of astressin, we assumed that a particular surface of the alpha-helix was important for binding to the receptor. The small peptide containing d-Ala31 and cyclohexylalanine38 on that surface was as potent as astressin in binding to the CRF receptor and showed significant ACTH suppression when administered to rats.

MeSH terms

  • Adrenocorticotropic Hormone / antagonists & inhibitors
  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Protein Structure, Secondary
  • Rats
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Structure-Activity Relationship


  • Oligopeptides
  • Receptors, Corticotropin-Releasing Hormone
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone