促肾上腺皮质激素拮抗剂
ACTH antagonists.
作者信息
Hofmann K, Montibeller J A, Finn F M
出版信息
Proc Natl Acad Sci U S A. 1974 Jan;71(1):80-3. doi: 10.1073/pnas.71.1.80.
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.
促肾上腺皮质激素（ACTH）分子活性位点内的结构修饰产生了一些类似物，这些类似物可抑制牛肾上腺皮质质膜上的激素敏感腺苷酸环化酶系统。已证明ACTH分子的色氨酸残基对于刺激该酶至关重要。用苯丙氨酸或N（α）-甲基色氨酸取代色氨酸，如在[谷氨酰胺（5），苯丙氨酸（9）]促肾上腺皮质激素（1-20）酰胺或[N（α）-甲基色氨酸（9）]促肾上腺皮质激素（1-24）中，可提供对ACTH受体具有高亲和力但无法激活腺苷酸环化酶系统的ACTH类似物。得出的结论是，仅对受体的亲和力不足以表达激素活性。拮抗剂不抑制由氟离子激活的肾上腺皮质腺苷酸环化酶这一观察结果表明，激素激活和氟激活是通过不同机制进行的。
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