Leucettamol A: a new inhibitor of Ubc13-Uev1A interaction isolated from a marine sponge, Leucetta aff. microrhaphis.
Leucettamol A: a new inhibitor of Ubc13-Uev1A interaction isolated from a marine sponge, Leucetta aff. microrhaphis.
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DOI：
10.1016/j.bmcl.2008.10.110
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发表时间：
2008-12
影响因子：
2.7
通讯作者：
S. Tsukamoto;Tomoharu Takeuchi;H. Rotinsulu;R. E. Mangindaan;R. V. VAN SOEST;K. Ukai;Hisayoshi Kobayashi;M. Namikoshi;T. Ohta;H. Yokosawa
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文献类型：
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作者：
S. Tsukamoto;Tomoharu Takeuchi;H. Rotinsulu;R. E. Mangindaan;R. V. VAN SOEST;K. Ukai;Hisayoshi Kobayashi;M. Namikoshi;T. Ohta;H. Yokosawa
从海绵Leucetta aff中分离到一种抑制泛素E2酶UBC13和Uev1a形成复合体的化合物。小轮虫。经波谱分析，该化合物为亮氨醇A(1)。用ELISA法检测其对UBC13-Uev1a相互作用的抑制作用，其IC50值为50μg/mL。该化合物是UBC13-Uev1A相互作用的第一个抑制剂，即UBC13的E2活性的第一个抑制剂。这些抑制剂被认为是抗癌药物的先导，可以上调肿瘤抑制蛋白P53的活性。有趣的是，1的氢化增强了它的抑制活性，IC50值为4μg/mL，而它的四乙酸酯衍生物没有活性，这表明1的羟基和/或氨基是抑制作用所必需的。
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 IC50value of 50μg/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 IC50value of 4μg/mL, while its tetraacetate derivative was inactive, indicating that the hydroxy and/or amino groups of 1 are required for the inhibition.