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Synthese des 17,18‐Diornithin‐β‐corticotropin‐(1–24)‐tetracosapeptides, eines biologisch aktiven Analogons des adrenocorticotropen Hormons
Author(s) -
Tesser G. I.,
Schwyzer R.
Publication year - 1966
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19660490302
Subject(s) - chemistry , arginine , ornithine , stereochemistry , amino acid , biological activity , in vitro , potency , in vivo , biochemistry , sequence (biology) , biology , microbiology and biotechnology
β‐Corticotropin (ACTH) possesses a striking sequence of basic amino‐acids‐Lys‐Lys‐Arg‐Arg‐ (No. 15–18) which is apparently necessary for the corticotropic activity: synthetic N‐terminal peptides containing this sequence are active, those lacking for example the two arginines as in the hexadecapeptide II [2] [3] [4] are essentially inactive. We have synthesized 17,18‐diornithine‐β‐corticotropin‐(1–24)‐tetracosapeptide (III), an analogue of the highly active β‐corticotropin‐(1–24)‐tetracosapeptide (I), in which the arginine residues 17 and 18 are replaced by ornithine. Quite unexpectedly this analogue is as highly potent in vitro (S AFFRAN & S CHALLY ) and in vivo (s.c. application, S AYERS test) as the tetracosapeptide with the ‘natural’ sequence. This equal potency holds also for lipotropic and melanotropic activity. We may conclude that the two guanidino groups of the arginines in pos. 17 and 18 are not essential for biological activity, but that they may be replaced by amino groups, as in ornithine. Due to the replacement of the guanidino groups by the more easily protectable amino group, the diornithine analogue III is more readily synthesized than the original diarginine polypeptide I.