Abstract
Derivatives of the epoxy-beta-aminoketone containing natural product eponemycin have been prepared in order to study the molecular mode of action of this anti-angiogenic compound. Synthesis and use of a biotinylated dihydroeponemycin analogue demonstrated that dihydroeponemycin forms a covalent adduct with at least two intracellular proteins in human endothelial cells. Pretreatment of cells with a five equivalent excess of dihydroeponemycin precluded biotin-dihydroeponemycin binding indicating a specific interaction between natural product and the target proteins. This biotin-dihydroeponemycin derivative will prove useful in the purification and identification of eponemycin receptors.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amides / metabolism
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Amides / pharmacology
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Animals
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Antibiotics, Antineoplastic / metabolism
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Antibiotics, Antineoplastic / pharmacology*
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Biotin / chemical synthesis*
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Biotin / chemistry
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Biotin / metabolism
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Biotin / pharmacology
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Cattle
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Cells, Cultured
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Electrophoresis, Polyacrylamide Gel
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism
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Humans
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Ligands
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Neovascularization, Physiologic / drug effects*
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Receptors, Drug / chemistry
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Receptors, Drug / metabolism
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Serine / analogs & derivatives*
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Serine / chemical synthesis
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Serine / chemistry
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Serine / metabolism
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Serine / pharmacology
Substances
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Amides
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Antibiotics, Antineoplastic
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Ligands
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Receptors, Drug
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biotin-dihydroeponemycin
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dihydroeponemycin
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eponemycin
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Serine
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Biotin