Modular synthesis of biologically active phosphatidic acid probes using click chemistry.
Modular synthesis of biologically active phosphatidic acid probes using click chemistry.
复制标题
使用点击化学模块化合成生物活性磷脂酸探针。
DOI：
10.1039/b901420a
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发表时间：
2009
影响因子：
--
通讯作者：
Best,MichaelD
中科院分区：
文献类型：
--
作者：
Smith,MatthewD;Sudhahar,ChristopherG;Gong,Denghuang;Stahelin,RobertV;Best,MichaelD
Phosphatidic acid (PA) is an important signaling lipid that plays roles in a range of biological processes including both physiological and pathophysiological events. PA is one of a number of signaling lipids that can act as site-specific ligands for protein receptors in binding events that enforce membrane association and generally regulate both receptor function and subcellular localization. However, elucidation of the full scope of PA activities has proven problematic, primarily due to the lack of a consensus sequence among PA-binding receptors. Thus, experimental approaches, such as those employing lipid probes, are necessary for characterizing interactions at the molecular level. Herein, we describe an efficient modular approach to the synthesis of a range of PA probes that employs a late stage introduction of reporter groups. This strategy was exploited in the synthesis of PA probes bearing fluorescent and photoaffinity tags as well as a bifunctional probe containing both a photoaffinity moiety and an azide as a secondary handle for purification purposes. To discern the ability of these PA analogs to mimic the natural lipid in protein-binding properties, each compound was incorporated into vesicles for binding studies using a known PA receptor, the C2 domain of PKCα. In these studies, each compound exhibited binding properties that were comparable to those of synthetic PA, indicating their viability as probes for effectively studying the activities of PA in cellular processes.
