title: Alpha-melanocyte stimulating hormone message and inhibitory sequences: comparative structure-activity studies on melanocytes.
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.
authors.affiliation: Peptide Therapeutics & Core Facility, Upjohn Company, Kalamazoo, MI 49001.
authors.forename: T K
authors.initials: TK
authors.lastname: Sawyer
authors.forename: D J
authors.initials: DJ
authors.lastname: Staples
authors.forename: A M
authors.initials: AM
authors.lastname: Castrucci
authors.forename: M E
authors.initials: ME
authors.lastname: Hadley
authors.forename: F A
authors.initials: FA
authors.lastname: al-Obeidi
authors.forename: W L
authors.initials: WL
authors.lastname: Cody
authors.forename: V J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D008116:Lizards; D008544:Melanocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011894:Rana pipiens; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D000521:alpha-MSH