Prestwich Glenn D
Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, UT 84108-1257, USA.
Prostaglandins Other Lipid Mediat. 2005 Sep;77(1-4):168-78. doi: 10.1016/j.prostaglandins.2004.09.018. Epub 2004 Nov 23.
Cells signal through lipids that are produced by phospholipid (PL) and phosphoinositide (PIPn) metabolism involve three enzymatic processes: (i) ester and phosphodiester hydrolysis by phospholipases, (ii) monophosphate hydrolysis by phosphatases, and (iii) phosphorylation of hydroxy groups by kinases. Unregulated enzyme activity correlates with specific pathologies, which are specific targets for therapeutic intervention. A variety of reagents now permit monitoring of in vitro enzyme activity, spatiotemporal changes of intracellular lipid concentrations, and identification of lipid-protein interactions. This minireview summarizes a chemical biology approach that illustrates how chemically synthesized affinity probes can be used to characterize changes in lipid signaling in cellular and molecular biology.
细胞通过磷脂(PL)和磷酸肌醇(PIPn)代谢产生的脂质进行信号传导,这涉及三个酶促过程:(i)磷脂酶进行酯和磷酸二酯水解,(ii)磷酸酶进行单磷酸水解,以及(iii)激酶进行羟基磷酸化。酶活性失调与特定疾病相关,这些疾病是治疗干预的特定靶点。现在有多种试剂可用于监测体外酶活性、细胞内脂质浓度的时空变化以及脂质-蛋白质相互作用的鉴定。本综述总结了一种化学生物学方法,该方法说明了如何使用化学合成的亲和探针来表征细胞和分子生物学中脂质信号传导的变化。