Synthesis of corticotropin peptides. XII. The effect of amino-terminal substitution in the corticotropin 1-18 peptide

The synthesis and biological properties are described of an octadecapeptide amide, alpha-amino-isobutyryl-tyrosyl-seryl-methionyl-glutamyl-histidyl-phenylalanyl -arginyl-tryptophyl-glycyl-lysylprolyl-valyl-glycyl-lysyl-lysyl-arginyl-arginine amide, corresponding to the first eighteen amino acid residues of corticotropin (ACTH) except for the amino terminal residue. The amino-terminal decapepticle as intermediate is built up from a tripeptide (positions 1-3) and a heptapeptide (4-10), where a benzyloxycarbonyl and a benzyl ester groups are used for protection of the terminal alpha-amino group and the gamma-carboxyl group of 5-glutamic acid, respectively. These protecting groups are removed in the final step with hydrogen fluoride. The new method is successfully applied to the corresponding 1-beta-alanine octadecapeptide amide, which has been synthesized previously by a different procedure. Adrenal-stimulating properties of the 1-alpha-aminoisobutyric acid peptide are compared with those of the 1-beta-alanine peptide to show that the former peptide is more active than the latter when assayed by the adrenal-ascorbic acid depletion and the in vivo steroidogenesis methods. The lipotropic activity of the new peptide is also shown to be more prolonged than that of the 1-beta-alanine peptide.