Potent and prolonged melanotropic activities of the alpha-MSH fragment analog, Ac-[Nle4,D-Phe7]-alpha-MSH4-9-NH2.
Ac-[Nle4, D-Phe7]-alpha-MSH4-9-NH2 and Ac-[Nle4]-alpha-MSH4-9-NH2, fragment analogs of the tridecapeptide, alpha-melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin), were synthesized. The potency and prolonged activity of the analogs were compared to alpha-MSH in several melanotropin bioassays. The D-Phe-containing hexapeptide was 10 times more active than alpha-MSH in stimulating melanoma tyrosinase activity. This analog was also 10-fold more potent than alpha-MSH in the lizard skin bioassay and about 10-fold less active in the frog skin bioassay. The melanotropic activity of Ac-[Nle4, D-Phe7]-alpha-MSH4-9-NH2 was considerably prolonged compared to alpha-MSH in each of the bioassays. These results demonstrate that the structural requirements for superpotency and prolonged activity of [Nle4, D-Phe7]-substituted analogs reside within this hexapeptide sequence.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D008116:Lizards; D009074:Melanocyte-Stimulating Hormones / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008545:Melanoma / Q000201:enzymology; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D011894:Rana pipiens; D012880:Skin Pigmentation / Q000187:drug effects*; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000031:analogs & derivatives*
D000596:Amino Acids; C049383:MSH(4-9)NH2, Ac-(Nle(4)-Phe(7))alpha-; D000521:alpha-MSH; D009074:Melanocyte-Stimulating Hormones; D014442:Monophenol Monooxygenase