Synthesis and analysis of potent cyclic analogs of the ACTH active center

Linear and cyclic analogues of the specific active center of the ACTH molecule have been synthesized, viz. [Lis5]ACTH-(5-10)-, [Lys5, cyclo (Gly10---epsilon Lys5)]-ACTH-(5-10)-hexapeptides, [Lys5 (Gly)]ACTH-(5-10)- and [Lys5, Gly11, cyclo (Gly11---epsilon Lys5)]-ACTH-(5-11)-heptapeptides. The cyclic...

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Bibliographic Details
Published inBioorganicheskaia khimiia Vol. 10; no. 6; p. 807
Main Authors Liepkaula, I K, Skuin'sh, A A, Romanovskiĭ, P Ia, Porunkevich, E A, Ratkevich, M P
Format Journal Article
LanguageRussian
Published Russia (Federation) 01.06.1984
Subjects
Adrenocorticotropic Hormone - analogs & derivatives
Adrenocorticotropic Hormone - chemical synthesis
Adrenocorticotropic Hormone - pharmacology
Animals
Binding Sites
Chemical Phenomena
Chemistry
In Vitro Techniques
Melanocytes - drug effects
Melanocytes - metabolism
Rana temporaria
Rats
Steroids - biosynthesis
Structure-Activity Relationship
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Summary:Linear and cyclic analogues of the specific active center of the ACTH molecule have been synthesized, viz. [Lis5]ACTH-(5-10)-, [Lys5, cyclo (Gly10---epsilon Lys5)]-ACTH-(5-10)-hexapeptides, [Lys5 (Gly)]ACTH-(5-10)- and [Lys5, Gly11, cyclo (Gly11---epsilon Lys5)]-ACTH-(5-11)-heptapeptides. The cyclic structures are fixed by covalent bond between the COOH-group of the C-terminal glycine and epsilon-amino group of a lysine residue. Azide method, DCC/HOBT or pentafluorophenyl esters are used for fragment coupling, while cyclization is achieved by means of diphenylphosphoryl azide or pentafluorophenyl esters. Cyclic compounds are 2-3 orders of magnitude more active than their linear counterparts as revealed by assaying their melanocyte-stimulating activity in vitro on frog skin. Only the title heptapeptide possesses a steroidogenic activity similar to that of ACTH-(5-10)-hexapeptide. The results obtained are in accord with the idea implying the formation in the hormone-receptor complexes of quasi-cyclic structures in the region of the specific active center of ACTH molecule.
ISSN:0132-3423