Fumagalone, a Reversible Inhibitor of Type 2 Methionine Aminopeptidase and Angiogenesis

摘要

Fumagillin and ovalicin constitute a family of structurally related natural products that possess antiangiogenic activity. We report the synthesis of a new fumagillin analogue, fumagalone, in which the spiroepoxide group is replaced with an aldehyde. Fumagalone inhibits type 2 methionine aminopeptidase (MetAP2) with IC_(50) = 8 μM and endothelial cell proliferation with IC_(50) = 52 nM. With dialysis and competition assays, it was unambiguously demonstrated that binding of fumagalone to MetAP2 is reversible.