Hormone‐Receptor Interactions. Demonstration of Two Message Sequences (Active Sites) in α‐Melanotropin

The purpose of this investigation was to elucidate the biological significance of the tripeptide sequence 11–13, ‐Lys‐Pro‐Val · NH 2 contained in α‐melanocyte‐stimulating hormone. To this end the in vitro melanotropic activities of 21 synthetic peptides related to the hormone were determined and compared with one‐another and with results reported in the literature. The tripeptide amide, H · Lys‐Pro‐Val · NH 2 , its N α ‐acetylderivative, and ‐weakly, but distinctly‐N α ‐acetyl‐L‐lysine‐amide were found to be hormonally active. The following conclusions were drawn: (1) α‐melanophore‐stimulating hormone possesses two message sequences (active sites), ‐Met‐Glu‐His‐Phe‐Arg‐Trp‐Gly‐, and ‐Lys‐Pro‐Val · NH 2 which are capable of independently triggering the hormone receptor responsible for melanin dispersion. (2) In correct covalent combination, the two message sequences act in a ‘cooperative’ manner to potentiate their activities on the receptors. (3) ‐Lys‐Pro‐Val‐ is an address sequence in adrenocorticotropic hormone and a message sequence in α‐melanocyte‐stimulating hormone. This implies that the two receptors (adrenal and melanocyte), albeit recognizing ‐Met‐Glu‐His‐Phe‐Arg‐Trp‐Gly‐ as stimulus, differ fundamentally in their response to ‐Lys‐Pro‐Val‐.