title: Alpha-melanotropin: the minimal active sequence in the lizard skin bioassay.
abstract: alpha-Melanotropin (alpha-melanocyte-stimulating hormone, alpha-MSH) is a tridecapeptide, Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. The minimal sequence of alpha-MSH required for agonism in the lizard (Anolis carolinensis) skin bioassay was determined to be Ac-His-Phe-Arg-Trp-NH2 (Ac-alpha-MSH6-9-NH2). Smaller fragments of this sequence (Ac-alpha-MSH6-8-NH2, Ac-alpha-MSH6-7-NH2, Ac-alpha-MSH7-9-NH2, and Ac-alpha-MSH7-8-NH2) were devoid of melanotropic activity. The tetrapeptide, Ac-alpha-MSH7-10-NH2, was also inactive, thus again demonstrating the importance of His at position 6 for minimal activity. The important potentiating amino acids were found to be Met-4, Lys-11, and Pro-12, since Ac-alpha-MSH4-10-NH2 was about 100 times more potent than Ac-alpha-MSH5-10-NH2, and Ac-[Nle4]-alpha-MSH4-11-NH2 was about 40 times more potent than Ac-alpha-MSH4-10-NH2 or Ac-[Nle4]-alpha-MSH4-10-NH2. Ac-alpha-MSH4-12-NH2 and Ac-[Nle4]-alpha-MSH4-12-NH2 were equipotent and about six times more potent than alpha-MSH. Since [Nle4]-alpha-MSH and Ac-[Nle4]-alpha-MSH4-13-NH2 were both equipotent but about sixfold less active than Ac-[Nle4]-alpha-MSH4-12-NH2, it is clear that valine at position 13 does not contribute to the potency of alpha-MSH, except possibly in a negative way. The minimal message sequence for equipotency to alpha-MSH appears to be Ac-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-NH2, since the analog, Ac-[Nle4]-alpha-MSH4-11-NH2, was as active as the native hormone. Ser-1, Tyr-2, Ser-3, Glu-5, and Val-13 are not important for melanotropic potency since Ac-alpha-MSH4-12-NH2 was more potent than alpha-MSH, and Ac-alpha-MSH5-10-NH2 and Ac-alpha-MSH6-10-NH2 were equipotent, being about 4,000 times less active than alpha-MSH.
authors.affiliation: Departamento de Fisiologia, Universidade de São Paulo, Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: Castrucci
authors.forename: M E
authors.initials: ME
authors.lastname: Hadley
authors.forename: T K
authors.initials: TK
authors.lastname: Sawyer
authors.forename: B C
authors.initials: BC
authors.lastname: Wilkes
authors.forename: F
authors.initials: F
authors.lastname: al-Obeidi
authors.forename: D J
authors.initials: DJ
authors.lastname: Staples
authors.forename: A E
authors.initials: AE
authors.lastname: de Vaux
authors.forename: O
authors.initials: O
authors.lastname: Dym
authors.forename: M F
authors.initials: MF
authors.lastname: Hintz
authors.forename: J P
authors.initials: JP
authors.lastname: Riehm
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D008116:Lizards; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis; D012867:Skin / Q000032:analysis; D013329:Structure-Activity Relationship; D000521:alpha-MSH
chemical_list: D010446:Peptide Fragments; D000521:alpha-MSH