Synthesis of enantiopure 2-carba-cyclic phosphatidic acid and effects of its chirality on biological functions
Synthesis of enantiopure 2-carba-cyclic phosphatidic acid and effects of its chirality on biological functions
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DOI：
10.1016/j.bbalip.2011.01.003
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发表时间：
2011-04-01
影响因子：
4.8
通讯作者：
Murakami-Murofushi, Kimiko
中科院分区：
文献类型：
--
作者：
Nozaki, Emi;Gotoh, Mari;Murakami-Murofushi, Kimiko
环磷脂酸(CPA)是一种天然存在的磷脂介体，它在甘油骨架的sn-2和sn-3位置上有一个非常独特的环磷酸环。我们设计并化学合成了几种代谢稳定的CPA衍生物。2-Carba-CPA(2ccPA)是一种在sn-2位用亚甲基取代磷酸氧的合成化合物，具有比天然CPA更强的生物活性。在这里，我们开发了一种合成2ccPA对映体的新方法。研究2ccPA对映体对自体趋化蛋白(ATX)活性、癌细胞侵袭和伤害性反射的影响。以及外消旋-2ccPA。两种对映体对ATX活性、癌细胞侵袭和伤害性反射均有抑制作用。由于它们的作用没有显著差异，2ccPA的手性可能不是2ccPA这些生物学功能的关键。(C)2011爱思唯尔B.V.保留所有权利。
Cyclic phosphatidic acid (CPA) is a naturally occurring phospholipid mediator, which has a quite unique cyclic phosphate ring at sn-2 and sn-3 positions of the glycerol backbone. We have designed and chemically synthesized several metabolically stabilized derivatives of cPA. 2-Carba-cPA (2ccPA) is one of the synthesized compounds in which the phosphate oxygen was replaced with a methylene group at the sn-2 position, and it showed much more potent biological activities than natural cPA. Here, we developed a new method of 2ccPA enantiomeric synthesis. And we examined the effects of 2ccPA enantiomers on autotaxin (ATX) activity, cancer cell invasion and nociceptive reflex. As well as racemic-2ccPA. both enantiomers showed inhibitory effects on ATX activity, cancer cell invasion and nociceptive reflex. As their effects were not significantly different from each other, the chirality of 2ccPA may not be critical for these biological functions of 2ccPA. (C) 2011 Elsevier B.V. All rights reserved.