ACTH antagonists.

K Hofmann; J A Montibeller; F M Finn

doi:10.1073/pnas.71.1.80

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ACTH antagonists.

K Hofmann·J A Montibeller·F M Finn

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Abstract

Structural modifications within the active site of the ACTH molecule have produced analogs that inhibit the hormone sensitive adenylate cyclase system of bovine adrenal cortical plasma membranes. It is demonstrated that the tryptophan residue of the ACTH molecule is essential for stimulation of the enzyme. Substitution of tryptophan by phenylalanine or by N(alpha)-methyltryptophan as in [Gln(5), Phe(9)]corticotropin(1-20) amide or [N(alpha)-Metrp(9)]corticotropin(1-24) provides ACTH analogs that exhibit high affinity for the ACTH receptor(s) but fail to activate the adenylate cyclase system. It is concluded that affinity for the receptors alone is not sufficient for expression of hormonal activity. The observation that adrenal cortical adenylate cyclase activated by fluoride ion is not inhibited by the antagonists indicates that hormonal and fluoride activation proceed via different mechanisms.

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Adenylyl Cyclases Adrenal Glands Adrenocorticotropic Hormone Amino Acid Sequence Animals Binding Sites Cattle Cell Membrane Cyclic AMP Enzyme Activation Fluorides In Vitro Techniques Receptors, Cell Surface Stimulation, Chemical Structure-Activity Relationship Journal Article

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K Hofmann, J A Montibeller, F M Finn. 1974. ACTH antagonists.. https://doi.org/10.1073/pnas.71.1.80

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