Proteasome inhibition by the natural products epoxomicin and dihydroeponemycin: insights into specificity and potency

While two structurally related epoxyketone-containing antitumor Natural Products, epoxomicin and eponemycin, share the Proteasome as a common intracellular target, they differ in their antiproliferative activity, Proteasome subunit binding specificity, and rates of Proteasome inhibition. As a first step towards understanding such differences and developing novel Proteasome subunit-specific inhibitors, we report here the synthesis and characterization of epoxomicin/dihydroeponemycin chimerae.