Combinatorial diffusion assay used to identify topically active melanocyte-stimulating hormone receptor antagonists.
alpha-Melanocyte-stimulating hormone (alpha-MSH) is implicated in pigmentation, central nervous system and immune system functions, growth, mitogenesis, and melanoma. Evaluation of these roles has been hindered by the lack of alpha-MSH antagonists. A combinatorial chemistry-based diffusion assay is used to find random tripeptides that antagonize normal frog and human melanoma MSH receptors and to identify pharmacological groups responsible for receptor interaction. The alpha-MSH antagonist D-Trp-Arg-Leu-NH2 is used to demonstrate directly the contribution of MSH to normal skin tone in frogs following injection or topical application.
Quillan
J M
JM
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06536-0812, USA.
Jayawickreme
C K
CK
Lerner
M R
MR
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004058:Diffusion; D015195:Drug Design; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008545:Melanoma; D008547:Melanophores / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D012867:Skin / Q000187:drug effects; D012879:Skin Physiological Phenomena; D012880:Skin Pigmentation / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D009842:Oligopeptides; D011979:Receptors, Pituitary Hormone; C029446:MSH receptor; D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP