Tsukamoto Sachiko, Takeuchi Tomoharu, Rotinsulu Henki, Mangindaan Remy E P, van Soest Rob W M, Ukai Kazuyo, Kobayashi Hisayoshi, Namikoshi Michio, Ohta Tomihisa, Yokosawa Hideyoshi
Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Bioorg Med Chem Lett. 2008 Dec 15;18(24):6319-20. doi: 10.1016/j.bmcl.2008.10.110. Epub 2008 Oct 31.
A compound that inhibits the formation of a complex composed of the ubiquitin E2 enzyme Ubc13 and Uev1A was isolated from the marine sponge Leucetta aff. microrhaphis. The compound was identified as leucettamol A (1) by spectroscopic analysis. Its inhibition of Ubc13-Uev1A interaction was tested by the ELISA method, revealing an IC(50) value of 50 microg/mL. The compound is the first inhibitor of Ubc13-Uev1A interaction, that is, that of the E2 activity of Ubc13. Such inhibitors are presumed to be leads for anti-cancer agents that upregulate activity of the tumor suppressor p53 protein. Interestingly, hydrogenation of 1 increased its inhibitory activity with an IC(50) value of 4 microg/mL, while its tetraacetate derivative was inactive, indicating that the hydroxy and/or amino groups of 1 are required for the inhibition.
从海洋海绵近微刺白枝海绵（Leucetta aff. microrhaphis）中分离出一种能抑制由泛素E2酶Ubc13和Uev1A组成的复合物形成的化合物。通过光谱分析将该化合物鉴定为白枝海绵醇A（1）。采用酶联免疫吸附测定（ELISA）法检测其对Ubc13-Uev1A相互作用的抑制作用，结果显示半数抑制浓度（IC50）值为50微克/毫升。该化合物是Ubc13-Uev1A相互作用的首个抑制剂，即Ubc13的E2活性的抑制剂。这类抑制剂被认为是上调肿瘤抑制蛋白p53活性的抗癌药物的先导化合物。有趣的是，化合物1氢化后其抑制活性增强，IC50值为4微克/毫升，而其四乙酸酯衍生物无活性，这表明化合物1的羟基和/或氨基是产生抑制作用所必需的。
