Zhou Guochun, Tsai Chiawei W, Liu Jun O
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
J Med Chem. 2003 Jul 31;46(16):3452-4. doi: 10.1021/jm0341103.
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 microM 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.
烟曲霉素和椭圆玫瑰树碱构成了一类具有抗血管生成活性的结构相关天然产物。我们报道了一种新的烟曲霉素类似物烟曲醛的合成，其中螺环氧基团被醛基取代。烟曲醛抑制2型甲硫氨酸氨肽酶（MetAP2）的IC50为8微摩尔，抑制内皮细胞增殖的IC50为52纳摩尔。通过透析和竞争试验，明确证明了烟曲醛与MetAP2的结合是可逆的。
