Squaryl group modified phosphoglycolipid analogs as potential modulators of GPR55
Squaryl group modified phosphoglycolipid analogs as potential modulators of GPR55
复制标题
方烷基修饰的磷酸糖脂类似物作为 GPR55 的潜在调节剂
DOI：
10.1039/c8cc04467h
复制
发表时间：
2018
影响因子：
4.9
通讯作者：
Ito Yukishige
中科院分区：
文献类型：
--
作者：
Ding Feiqing;Guy Adam T.;Greimel Peter;Hirabayashi Yoshio;Kamiguchi Hiroyuki;Ito Yukishige
溶血磷脂酰葡糖苷（LPGlc）是一种结构独特的糖脂，其通过激活脊髓感觉轴突的A类G蛋白偶联受体（GPR）55而在中枢神经系统发育期间充当用于延伸轴突的引导线索。GPR 55不仅在发育过程中发挥重要作用，而且还与许多疾病状态有关，使靶向GPR 55的分子受到广泛关注。在这项研究中，我们开发了一种新型的LPGlc类似物的合成途径，其特征在于方芳基二酰胺基团作为磷酸二酯的替代物。我们报告了一系列LPGlc类似物的简易合成，它们的GPR依赖的生物活性和关于GPR 55调节的结构-活性关系的系统分析。与天然LPGlc相比，在所有立体中心具有相同构型的先导化合物表现出排斥背根神经节（DGR）伤害感受神经元的轴突的活性。
Lysophosphatidyl glucoside (LPGlc) is a structurally unique glycolipid that acts as a guidance cue for extending axons during central nervous system development by activating the class A G protein coupled receptor (GPR) 55 of spinal cord sensory axons. GPR55 not only plays an important role during development, but is also implicated in many disease states, rendering molecules that target GPR55 of widespread interest. In this study, we developed synthetic access to a novel class of LPGlc analogues featuring a squaryl diamide group as surrogate for the phosphodiester. We report the facile synthesis of a series of LPGlc analogues, their GPR dependent biological activity and a systematic analysis of the structure–activity relationship in regards to GPR55 modulation. The lead compound featuring identical configuration at all stereocenters compared to natural LPGlc exhibits an activity to repel axons of dorsal root ganglion (DGR) nociceptive neurons.