Potent and prolonged melanotropic activities of the α-MSH fragment analog, Ac-[Nle4, D-Phe7]-α-MSH4–9-NH2

Ac-[Nle 4 , D -Phe 7 ]-α-MSH 4–9 -NH 2 and Ac-[Nle 4 ]-α-MSH 4–9 -NH 2 , fragment analogs of the tridecapeptide, α-melanocyte stimulating hormone (α-MSH, α-melanotropin), were synthesized. The potency and prolonged activity of the analogs were compared to α-MSH in several melanotropin bioassays. The D -Phe-containing hexapeptide was 10 times more active than α-MSH in stimulating melanoma tyrosinase activity. This analog was also 10-fold more potent than α-MSH in the lizard skin bioassay and about 10-fold less active in the frog skin bioassay. The melanotropic activity of Ac-[Nle 4 , D -Phe 7 ]-α-MSH 4–9 -NH 2 was considerably prolonged compared to α-MSH in each of the bioassays. These results demonstrate that the structural requirements for superpotency and prolonged activity of [Nle 4 , D -Phe 7 ]-substituted analogs reside within this hexapeptide sequence.