Synthesis of Corticotropin Peptides. IX. Synthesis of [1-Glycine]-ACTH(1–18)-Octadecapeptide Amide

Abstract

The synthesis is decribed of an octadecapeptide, glycyl-tyrosyl-seryl-methionyl-glutamyl-histidyl-phenyl-alanyl-arginyl-tryptophyl-glycyl-lysyl-prolyl-valyl-glycyl-lysyl-lysyl-arginyl-arginine amide, corresponding to the first eighteen amino acid residues of corticotropin except for the amino end which has been replaced by a glycine for the serine in the native hormone. The protected end product was obtained by two different coupling procedures, the active ester and the catalyzed carbodiimide, from the amino-terminal decapeptide and the octapeptide of carboxyl end. The over-all yields of the peptide, for the final coupling, deblocking and purification steps, in the active ester and the carbodiimide procedures were approximately forty and thirty per cent, respectively. The synthetic octadecapeptide amide has been shown to possess a high adrenal corticotropic activity, which is comparable to that of the corresponding 1-serine octadecapeptide amide, and a lipolytic activity which is significantly lower than that of the 1-serine analog.

Structure-Activity Relationships of Synthetic Adrenocorticotropic Octadecapeptides with Special Reference to Biological Half-Life

“…The adrenocorticotropic potencies of the eight octadecapeptide analogues and purified sheep ACTH were estimated against the third USP Corticotropin Reference Standard using the six different methods (Table 2). As reported previously (Otsuka et al, 1970a) peptide I having the first 18 amino acid sequence of native ACTH and acidic carboxyl terminal, shows only 1/10-1/20 of the activity of native ACTH. But peptide II, having an amide group at the carboxyl-terminal had almost the same iv potency as native ACTH.…”

Effect of Synthetic Corticotropins on Human Growth Hormone Secretion

“…This report showed that HGH secretion was caused by the administration of Glyl-ACTH (1-18) octadecapeptide amide (50022-S) which was synthetized by Otsuka et al (Otsuka et al, 1970).…”