EPONEMYCIN ANALOGS - SYNTHESES AND USE AS PROBES OF ANGIOGENESIS

Derivatives of the epoxy-beta-aminoketone containing natural product e ponemycin have been prepared in order to study the molecular mode of a ction of this anti-angiogenic compound. Synthesis and use of a biotiny lated dihydroeponemycin analogue demonstrated that dihydroeponemycin f orms a covalent adduct with at least two intracellular proteins in hum an endothelial cells. Pretreatment of cells with a five equivalent exc ess of dihydroeponemycin precluded biotin-dihydroeponemycin binding in dicating 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. (C) 19 98 Elsevier Science Ltd. All rights reserved.