Synthetic peptide KKRR corresponding to the human ACTH fragment 15-18 is an antagonist of the ACTH receptor

• Published in: Russian journal of bioorganic chemistry Vol. 34; no. 1; pp. 24 - 29
• Main Authors: Kovalitskaya, Yu. A, Kolobov, A. A, Kampe-Nemm, E. A, Zolotarev, Yu. A, Yurovskii, V. V, Sadovnikov, V. B, Lipkin, V. M, Navolotskaya, E. V
• Format: Journal Article
• Language: English
• Published: Dordrecht Dordrecht : SP MAIK Nauka/Interperiodica 2008; SP MAIK Nauka/Interperiodica
• Subjects: adenylate cyclase; adrenal cortex; adrenocorticotropic hormone (ACTH); Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Life Sciences; Organic Chemistry; peptides; receptors; peptides; adrenocorticotropic hormone (ACTH); receptors; adrenal cortex; adenylate cyclase
• ISSN: 1068-1620; 1608-330X; 1573-9163
• DOI: 10.1134/S1068162008010020

Tritium-labeled synthetic fragments of human adrenocorticotropic hormone (ACTH) [³H]ACTH (11-24) and [³H]ACTH (15-18) with a specific activity of 22 and 26 Ci/mmol, respectively, were obtained. It was found that [³H]ACTH-(11-24) binds to membranes of the rat adrenal cortex with high affinity and high specificity (K d 1.8 ± 0.1 nM). Twenty nine fragments of ACTH (11-24) were synthesized, and their ability to inhibit the specific binding of [³H]ACTH (11-24) to adrenocortical membranes was investigated. The shortest active peptide was found to be an ACTH fragment (15-18) (KKRR) (K i 2.3 ± 0.2 nM), whose [³H] labeled derivative binds to rat adrenocortical membranes (K d 2.1 ± 0.1 nM) with a high affinity. The specific binding of [³H]ACTH-(15-18) was inhibited by 100% by unlabeled ACTH (11-24) (K i 2.0 ± 0.1 nM). ACTH (15-18) in the concentration range of 1-1000 nM did not affect the adenylate cyclase activity of adrenocortical membranes and, therefore, is an antagonist of the ACTH receptor.