Synthese eines Tetracosapeptides mit hoher corticotroper Wirksamkeit: β^1–24‐Corticotropin

A new scheme for the protection of amino and carboxyl groups in the side chains of amino-acid residues was developed and led to a blocked tetracosapeptide II which contains only protective groups derived from t-butanol.

Abstract

Abstract The synthesis of the tetracosapeptide β 1–24 ‐corticotropin, containing the N‐terminal 24 amino‐acid residues of β‐corticotropin (ACTH) 2 ), is described in detail. Many intermediates, including derivatives of the decapeptide β 1–10 ‐corticotropin and of the tetradecapeptide β 11–24 ‐corticotropin, were obtained in the cristalline state. A new scheme for the protection of amino and carboxyl groups in the side chains of amino‐acid residues was developed: this led to a blocked tetracosapeptide II which contains only protective groups derived from t ‐butanol. These may be removed quantitatively, without formation of side‐products. β 1–24 ‐Corticotropin (I) is thus obtained directly in an analytically pure state; [α] 25 = − 88,6 ± 2° (c = 0,5 in 1 per cent acetic acid). The biological activity of the product was found to be 106 ± 14 USP‐U/mg (ACTH). It is equally active on intravenous application in human beings.