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THE MESSAGE SEQUENCE OF α‐MELANOTROPIN: DEMONSTRATION OF TWO ACTIVE SITES
Author(s) -
EBERLE ALEX,
SCHWYZER ROBERT
Publication year - 1976
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1976.tb03814.x
Subject(s) - tetrapeptide , tripeptide , pentapeptide repeat , receptor , melanocyte stimulating hormone , hormone , chemistry , biological activity , stereochemistry , endocrinology , medicine , in vitro , oligopeptide , biology , biochemistry , peptide
SUMMARY The purpose of this investigation was to elucidate the biological significance of lysine 11 and of the tripeptide sequence ‐Lys‐Pro‐Val‐NH 2 for the biological activity of α‐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 lysine 11 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: α‐MSH possesses (in contrast to ACTH) two message sequences (active sites), (i) ‐Glu‐His‐Phe‐Arg‐Trp‐, and (ii) ‐Gly‐Lys‐Pro‐Val‐NH 2 which are capable of independently triggering the hormone receptor responsible for melanin dispersion. Thus, despite the close structural similarity of the two hormones, α‐MSH and ACTH appear to react with their respective target cell receptors by quite different chemical mechanisms, implying different receptor structures.