Alpha-melanocyte stimulating hormone message and inhibitory sequences: comparative structure-activity studies on melanocytes.
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.
Sawyer
T K
TK
Peptide Therapeutics & Core Facility, Upjohn Company, Kalamazoo, MI 49001.
Staples
D J
DJ
Castrucci
A M
AM
Hadley
M E
ME
al-Obeidi
F A
FA
Cody
W L
WL
Hruby
V J
VJ
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*
D010446:Peptide Fragments; D000521:alpha-MSH