PT - JOURNAL ARTICLE AU - J D Moyer AU - O Reizes AU - S Ahir AU - C Jiang AU - N Malinowski AU - D C Baker TI - Substrate properties of analogs of myo-inositol. DP - 1988 Jun 01 TA - Molecular Pharmacology PG - 683--689 VI - 33 IP - 6 4099 - http://molpharm.aspetjournals.org/content/33/6/683.short 4100 - http://molpharm.aspetjournals.org/content/33/6/683.full SO - Mol Pharmacol1988 Jun 01; 33 AB - The hydrolysis of the minor cell membrane lipid phosphatidylinositol-4,5-bisphosphate mediates the action of many growth factors and hormones. As an approach to the development of specific inhibitors of this process, we have synthesized a series of analogs of myo-inositol and have evaluated their ability to serve as substrates for phosphatidylinositol synthetase. Modification at the 2-, 3-, or 4-positions produced compounds unable to serve as substrates, but several 5-modified analogs retained activity as substrates of phosphatidylinositol synthetase. The product formed from 5-deoxy-5-fluoro-myo-[3H]inositol by phatidylinositol synthetase was hydrolyzed by phospholipase D and gave 5-deoxy-5-fluoro-myo-inositol as the radiolabeled product. Two analogs, 5-deoxy-myo-inositol and 5-deoxy-5-fluoro-myo-inositol, were shown to permeate L1210 leukemia cells and be incorporated into cellular phospholipid. Analysis of the radiolabeled lipids formed on incubation of L1210 cells with 5-deoxy-5-fluoro-myo-[3H]inositol indicated that the fradulent lipid formed was further phosphorylated to the monophosphate but not to the diphosphate form.