Development and mechanistic study of novel anti- Alzheimer's disease drugs with PKC-ε selective activation

我们已经有了利用脂肪酶介导的拆分方法制备对映体纯DCP-LA的所有四种异构体的合成路线，并找到了最具活性的立体异构体。然而，第一条合成路线难以实现光学活性DCP-LA的克级合成。在本研究中，我们建立了克级制备DCP-LA对映体纯的四种异构体的合成路线，并找到了在体内体系中最活跃的立体异构体。此外，我们还发现新的游离脂肪酸衍生物HUHS2002激活了α7 ACh受体反应。此外，我们还利用亲和层析的方法对DCP-LA的部分候选目的蛋白进行了鉴定。

We have already synthetic route for the preparation of all of the four isomers of enantiomerically pure DCP-LA employing lipase-mediated resolution method, and found the most active stereoisomers. However, first synthetic route was difficult for gram-scale synthesis of optically active DCP-LA. In this research, we have developed synthetic route for gram-scale preparation of all of the four isomers of enantiomerically pure DCP-LA, and found the most active stereoisomers in vivo system. In addition, we found that novel free fatty acid derivative HUHS2002 activated α7 ACh receptor responces. Fuethemore, we identified some candidates of target protein of DCP-LA with affinity chromatography methods.