Selective acetylation of the terminal amino group of corticotrophin

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Abstract
The serine residues of corticotrophin A1 were O-acetylated by treatment with acetic acid containing HBr. Subsequent treatment with mild alkali moved one acetyl group to the terminal amino group, hydrolyzed the other and liberated amide ammonia. The product (N-acetylcortico-trophin A2) has been purified by ion-exchange chromatography and characterized. N-Acetylcorticotrophin A2 possesses less than 10% of the corticotrophic activity of corticotrophin A1. This result supports suggestions that a free amino group on the N-terminal serine residue is essential for high corticotrophic activity. N-Acetylcorticotrophin A2 possesses 5-10 times the melanocyte-stimulating activity of corticotrophin A1 when assayed on isolated frog skin. In the intact frog N-acetylcorticotrophin A2 possesses no more melanocyte-stimulating activity than corticotrophin A1 if the response is assessed up to 1 hr. after injection, but more than 10 times the activity if the response is assayed after 6 hr. [beta]-Melanocyte-stimulating hormone possesses about 100 times the melanocyte-stimulating activity of corticotrophin A1 if the response is assessed 1 hr. after injection into the frog, but much less if the assessment is made later. Comparison of the results of melanocyte-stimulating assays with chemical structure suggests that the potential activity of the sequence of [alpha]-melanocyte-stimulating hormone in N-acetylcorticotrophin A2 is inhibited by other structural features of its molecule.