Synthesis and biological activity of metabolically stabilized cyclopentyl trisphosphate analogues of D-myo-Ins(1,4,5)P3.
Synthesis and biological activity of metabolically stabilized cyclopentyl trisphosphate analogues of D-myo-Ins(1,4,5)P3.
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D-myo-Ins(1,4,5)P3 代谢稳定的环戊基三磷酸类似物的合成和生物活性。
DOI：
10.1002/cmdc.200700071
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发表时间：
2007
期刊：
影响因子：
3.4
通讯作者：
Prestwich,GlennD
中科院分区：
文献类型：
--
作者：
Zhang,Liuyin;Huang,Wei;Tanimura,Akihiko;Morita,Takao;Harihar,Sitaram;Dewald,DaryllB;Prestwich,GlennD
我们描述了基于已知的环戊烷五醇三(磷酸酯)2的四种新型代谢稳定的Ins(1,4,5)P3类似物的合成：三(硫代磷酸酯)3、三(亚甲基磷酸酯)4、三(磺酰胺)5和三(硫酸酯)6。在这些类似物中，只有三(硫代磷酸酯)3和母体三(磷酸酯)2与I型InsP3R构建体结合。此外，tris(硫代磷酸酯)3 和母体 tris(磷酸酯)2 都能在 MDA MB-435 乳腺癌细胞中引起钙释放。这两种化合物的 Ins(1,4,5)P3 激动剂活性可以根据配体与 I 型 InsP3R 结合域的计算对接合理化。
We describe the synthesis of four novel metabolically stabilized analogues of Ins(1,4,5)P3based on the known cyclopentane pentaol tris(phosphate)2: tris(phosphorothioate)3, tris(methylenephosphate)4, tris(sulfonamide)5, and tris(sulfate)6. Of these analogues, only the tris(phosphorothioate)3and parent tris(phosphate)2bound to the type I InsP3R construct. In addition, both the tris(phosphorothioate)3and parent tris(phosphate)2elicited calcium release in MDA MB‐435 breast cancer cells. The Ins(1,4,5)P3agonist activities of these two compounds can be rationalized on the basis of computational docking of the ligands to the binding domain of the type I InsP3R.