Alpha-melanocyte-stimulating hormone structure-activity studies: comparative analysis of melanotropic and CNS bioactivities.
The structure-activity relationships in vitro of alpha-MSH (alpha-melanocyte-stimulating hormone, alpha-melanotropin) analogs as determined on normal and transformed (melanoma cell) melanocyte bioassays are summarized. Specifically, the characterization of potent and metabolically stable melanotropic agonist analogs and a newly discovered antagonist of alpha-MSH are highlighted. Comparison of these data versus the known structure-activity relationships of alpha-MSH related to CNS bioactivities suggests the existence of nonclassical alpha-MSH receptor-mediated pathways or, perhaps, a yet undefined endogenous neuropeptidergic pathway(s) having different selectivities for alpha-MSH analogs. In summary, several of the alpha-MSH analogs reported here may be useful molecular probes in future strategies aimed at the identification and systematic characterization of both peripheral and central alpha-MSH receptors.
Sawyer
T K
TK
Biopolymer Chemistry-Peptide Therapeutics & Core Facility, Upjohn Company, Kalamazoo, Michigan 49001.
Hadley
M E
ME
Hruby
V J
VJ
Castrucci
A M
AM
Staples
D J
DJ
Farah
J
J
O'Donohue
T L
TL
D000595:Amino Acid Sequence; D000818:Animals; D008116:Lizards; D008544:Melanocytes / Q000166:cytology* / Q000187:drug effects; D008546:Melanoma, Experimental / Q000201:enzymology; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D011894:Rana pipiens; D012867:Skin / Q000166:cytology* / Q000187:drug effects; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000521:alpha-MSH; D014442:Monophenol Monooxygenase