Hormone-receptor interactions. The message sequence of alpha-melanotropin: demonstration of two active sites.

The purpose of this investigation was to elucidate the biological significance of lysine11 and of the tripeptide sequence =Lys-Pro-Val-NH2 for the biological activity of alpha-melanocyte-stimulating hormone. To this end the in vitro melanotropic activities of twenty-four synthetic peptides related to the hormone were determined. Extension or reduction of the length of the lysine11 side chain results in a marked decrease of the melanotropic potency of the respective analogue. The C-terminal tripeptide (11--13), the tetrapeptide (10--13), and the pentapeptide (9--13) were found to be hormonally active in the same order of magnitude as the central hexapeptide (5--10). The following conclusion was drawn: alpha-MSH possesses (in contrast to ACTH) two message sequences (active sites), (i)-Glu-His-Phe-Arg-Trp-, and (ii)-Gly-Lys-Pro-Val-NH2 which are capable of independently triggering the hormone receptor responsible for melanin dispersion. Thus, despite the close structural similarity of the two hormones, alpha-MSH and ACTH appear to react with their respective target cell receptors by quite different chemical mechanisms, implying different receptor structures.