Preference for Glucose over Inositol Headgroup during Lysolipid Activation of G Protein-Coupled Receptor 55
Preference for Glucose over Inositol Headgroup during Lysolipid Activation of G Protein-Coupled Receptor 55
复制标题
DOI：
10.1021/acschemneuro.8b00505
复制
发表时间：
2019-01-01
影响因子：
5
通讯作者：
Greimel, Peter
中科院分区：
文献类型：
--
作者：
Guy, Adam T.;Kano, Koki;Greimel, Peter
G蛋白偶联受体55（GPR 55）在脑和外周神经系统中高度表达。最初作为大麻素受体去乙酰化，最近GPRS 5已被描述为溶血磷脂反应性受体，特别是对溶血磷脂酰肌醇和溶血磷脂酰-β-n-葡萄糖苷（LysoPtdGlc）。为了表征溶血磷脂-GPR 55相互作用，利用基于磷（III）的化学方法建立LysoPtdGlc和所选类似物的合成途径。在初级感觉神经元中使用GPR 55依赖性趋化性测定来评估每种合成脂质的生物活性。结合分子动力学模拟，潜在的配体进入端口和结合口袋的细节进行了讨论。这些结果突出了葡萄糖-超过肌醇-和半乳糖-配置的头部基团的偏好。
G protein-coupled receptor 55 (GPR55) is highly expressed in brain and chemorepulsion peripheral nervous system. Originally deorphanized as a cannabinoid receptor, recently GPRS5 has been described as a lysophospholipid-responsive receptor, specifically toward lysophosphatidylinositol and lysophosphatidyl-beta-n-glucoside (LysoPtdGlc). To characterize lysolipid-GPR55 interaction, synthetic access to LysoPtdGlc and selected analogues was established utilizing a phosphorus(III)-based chemical approach. The biological activity of each synthetic lipid was assessed using a GPR55-dependent chemotropism assay in primary sensory neurons. Combined with molecular dynamics simulations the potential ligand entry port and binding pocket specifics are discussed. These results highlight the preference for gluco- over inositol- and galacto-configured headgroups.