Potentiation of the antagonistic effect of ACTH11-24 on steroidogenesis by synthesis of covalent dimeric conjugates.
Covalent dimerization of the adrenocorticotropin fragment ACTH11-24 increases its antagonistic potency on the ACTH-induced steroidogenesis in isolated bovine fasciculata/reticularis cells by 3 orders of magnitude when the C-termini are linked via a 10 A long spacer. This strong potentiation, probably mediated by cross-linking of the receptors, was shown to be dependent on the point of attachment of the monomeric fragment to the spacer, thus providing information about the position of the binding site in the hormonal segment and about the distance of the receptors on the cell surface.
Fauchère
J L
JL
Rossier
M
M
Capponi
A
A
Vallotton
M B
MB
D000311:Adrenal Glands / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003366:Cosyntropin; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D046911:Macromolecular Substances; D010446:Peptide Fragments / Q000494:pharmacology*; D011487:Protein Conformation; D013256:Steroids / Q000096:biosynthesis*; D013329:Structure-Activity Relationship
D046911:Macromolecular Substances; D010446:Peptide Fragments; D013256:Steroids; D003366:Cosyntropin; C034016:ACTH (11-24); D000324:Adrenocorticotropic Hormone