Relationships Between the Structure and Biological Activities of Corticotropin and Related Peptides: Alterations in the N-terminal Serine1

Abstract

Several peptides in which the N-terminal serine of corticotropin has been altered have been assayed relative to unaltered corticotropin A₁ for their biological activities, both adrenal and extra-adrenal. The adrenal activities assayed were in vivo steroidogenesis in 24-hr hypophysectomized rats and in vitro steroidogenesis by quartered rat adrenals. The in vitro release of free fatty acids by rat epididymal adipose tissue and the hypoglycemic effect in the intact mouse were the extra-adrenal activities assayed. Oxidative deamination of the free a-amino group by periodate was accompanied by a reduction of in vitro steroidogenic and lipolytic activity to 10%. in vivo steroidogenesis was more markedly reduced (to 1–2%) while in vivo hypoglycemia was greater than expected (32 %). Replacement of the N-terminal serine by an N-terminal glycine did not alter any of the measured activities. N-acetylation of the terminal serine resulted in a peptide which caused a marked reduction in all the activities studied. Thus, a free a-amino group is necessary for full activity. The absence of an αamino group results in a marked decrease in in vivo adrenal stimulating activity and only a modest decrease in in vivo extra-adrenal activity.