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.