Abstract
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.
MeSH terms
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Amino Acid Sequence
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Animals
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Cells, Cultured
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Cyclic AMP / metabolism
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Diffusion
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Drug Design
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Humans
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Melanocyte-Stimulating Hormones / pharmacology
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Melanoma
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Melanophores / cytology
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Melanophores / drug effects
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Melanophores / metabolism
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Molecular Sequence Data
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry
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Oligopeptides / pharmacology*
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Receptors, Pituitary Hormone / antagonists & inhibitors*
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Skin / drug effects
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Skin Physiological Phenomena
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Skin Pigmentation / drug effects
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Structure-Activity Relationship
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Tumor Cells, Cultured
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Xenopus laevis
Substances
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Oligopeptides
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Receptors, Pituitary Hormone
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MSH receptor
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Melanocyte-Stimulating Hormones
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Cyclic AMP