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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Jan;71(1):80–83. doi: 10.1073/pnas.71.1.80

ACTH Antagonists

Klaus Hofmann 1, Judith A Montibeller 1, Frances M Finn 1
PMCID: PMC387936  PMID: 4359333

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 Nα-methyltryptophan as in [Gln5, Phe9]corticotropin1-20 amide or [Nα-Metrp9]corticotropin1-24 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.

Keywords: ACTH receptor, adenylate cyclase, S-peptide-S-protein system, peptide hormones, adrenal cortical plasma membranes

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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