Eponemycin analogues: syntheses and use as probes of angiogenesis.
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.
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Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA.
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Crews
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D000577:Amides / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology*; D001710:Biotin / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008024:Ligands; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011955:Receptors, Drug / Q000737:chemistry / Q000378:metabolism; D012694:Serine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D000577:Amides; D000903:Antibiotics, Antineoplastic; D008024:Ligands; D011955:Receptors, Drug; C116211:biotin-dihydroeponemycin; C116212:dihydroeponemycin; C063282:eponemycin; D012694:Serine; D001710:Biotin