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.
Kim
K B
KB
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA.
Myung
J
J
Sin
N
N
Crews
C M
CM
D002455:Cell Division / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000187:drug effects* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D012694:Serine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013379:Substrate Specificity
D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D009842:Oligopeptides; C116212:dihydroeponemycin; D012694:Serine; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C078846:epoxomicin