Synthesis and Biological Activity of Actin-Depolymerizing Substances
Synthesis and Biological Activity of Actin-Depolymerizing Substances
复制标题
肌动蛋白解聚物质的合成及生物活性
DOI：
10.1002/chin.200722257
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
H. Kigoshi
中科院分区：
文献类型：
--
作者：
K. Suenaga;H. Kigoshi
海百合素a1是从海百合中分离得到的一种有效的抗肿瘤大环内酯类化合物。Aplyronine A与肌动蛋白相互作用，肌动蛋白是细胞骨架中的主要蛋白质之一。我们完成了阿普氨酸A及其18个类似物的全合成，并研究了其构效关系。用光亲和标记法分析了阿普赖氨酸类似物与肌动蛋白的相互作用，并对阿普赖氨酸a与肌动蛋白配合物的x射线晶体结构进行了分析。这些结果表明，aplyronine A在肌动蛋白亚结构域1和3之间的疏水性间隙与肌动蛋白结合。阿普氨酸A大内酯部分的结合方式不同于以往报道的大内酯类化合物。此外，aplyronine A的三甲基丝氨酸部分（对HeLa S3细胞具有细胞毒性的必需功能基团）从actin- aplyron9 A复合物的表面伸出。
Aplyronine A 1 is a potent antitumor macrolide isolated from the sea hare Aplysia kurodai. Aplyronine A interacts with actin, one of the major proteins in cytoskeleton. We achieved total synthesis of aplyronine A and its 18 analogs and investigated structure-activity relationships. Analysis of the interaction of aplyronine analogs with actin by a photoaffinity labeling method and X-ray crystal structure analysis of actin complex with aplyronine A have been carried out. These results revealed that aplyronine A binds to actin at the hydrophobic cleft between subdomains 1 and 3 of actin. The binding mode of the macrolactone part of aplyronine A was different from previously reported macrolides. In addition, the trimethylserine moiety of aplyronine A, the essential functional group for cytotoxicity against HeLa S3 cells, was sticking out from a surface of actin-aplyro-nine A complex.