Structural and functional organization of ACTH: synthesis and properties of analogs of ACTH- (11-24) -tetradeca- and ACTH- (1-24) -tetracosapeptides containing hexa-amino acids instead of a natural sequence of ACTH 19-24 amino acids
Syskov, I.V.; Romanovskiĭ, P.I.; Vosekalna, I.A.; Skuin'sh, A.A.; Ratkevich, M.P.
Bioorganicheskaia Khimiia 10(5): 618-625
1984
ISSN/ISBN: 0132-3423 PMID: 6093817 Document Number: 232055
To assess the role of amino acid sequence ACTH 19-24 in the corticotropin structure and steroidogenic activity, the analogues of ACTH-(11-24)-tetradeca- and ACTH-(1-24)-tetracosapeptides containing hexaglycine, hexaphenylalanine, hexaglutamic acid or hexalysine instead of the natural 19-24 sequence have been synthesized by conventional methods. All these compounds in water have the CD curves characteristic of random coil, CD spectra of analogue ACTH-(1-24)-tetracosapeptide and hexalysine-containing analogue ACTH-(11-24)-tetradecapeptide in trifluoroethanol indicate the presence of alpha-helices. The latter compound manifested higher steroidogenic activity than ACTH-(11-24)-tetradecapeptide. All the other analogues were either less active than ACTH-(1-24)-tetracosapeptide or inactive over the concentration range 10(-5)-10(2) mg/ml, thereby testifying to functional importance of the 19-24 sequence for manifesting full steroidogenic activity.