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

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 α-helix was important for binding to the receptor. The small peptide containing D-Ala 31 and cyclohexylalanine 38 on that surface was as potent as astressin in binding to the CRF receptor and showed significant ACTH suppression when administered to rats.