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Alpha-melanocyte stimulating hormone message and inhibitory sequences: comparative structure-activity studies on melanocytes.

T K Sawyer·D J Staples·A M Castrucci·M E Hadley·F A al-Obeidi·W L Cody·V J Hruby
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Abstract

We investigated the structure-activity relationships of alpha-MSH (alpha-melanocyte stimulating hormone) fragment derivatives of the generic formulae Ac-alpha-MSH(x-13)-NH2 and Ac-alpha-MSH(6-x)-NH2. The minimal C-terminal sequences required for melanotropic activity were 8-13 and 7-13, respectively, in the frog and lizard skin bioassays. The Arg8-Trp9 sequence appears to be a fundamental component of the minimal message sequences found to date such as alpha-MSH(6-9), alpha-MSH(8-13) and alpha-MSH(7-13). We discovered that Ac-alpha-MSH(7-10)-NH2 was a weak and selective alpha-MSH antagonist on the lizard skin bioassay. Analysis of alpha-MSH(7-10) analogues of the generic formula Ac-Xaa-Arg-Trp-Yaa-NH2 led to Ac-[D-Trp7,D-Phe10]alpha-MSH(7-10)-NH2, a moderately potent, specific and competitive inhibitor of alpha-MSH in both the frog and the lizard skin bioassays.

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Amino Acid SequenceAnimalsLizardsMelanocytesMolecular Sequence DataPeptide FragmentsRana pipiensStructure-Activity Relationshipalpha-MSHJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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T K Sawyer, D J Staples, A M Castrucci, M E Hadley, F A al-Obeidi, W L Cody, V J Hruby. Alpha-melanocyte stimulating hormone message and inhibitory sequences: comparative structure-activity studies on melanocytes.. https://doi.org/10.1016/0196-9781(90)90092-j

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