title: Substrate properties of analogs of myo-inositol.
abstract: 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.
authors.affiliation: Laboratory of Biological Chemistry, National Cancer Institute, Bethesda, MD 20892.
authors.forename: J D
authors.initials: JD
authors.lastname: Moyer
authors.forename: O
authors.initials: O
authors.lastname: Reizes
authors.forename: S
authors.initials: S
authors.lastname: Ahir
authors.forename: C
authors.initials: C
authors.lastname: Jiang
authors.forename: N
authors.initials: N
authors.lastname: Malinowski
authors.forename: D C
authors.initials: DC
authors.lastname: Baker
mesh_terms: D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase; D007294:Inositol / Q000031:analogs & derivatives* / Q000378:metabolism; D008958:Models, Molecular; D010743:Phospholipids / Q000378:metabolism; D010770:Phosphotransferases; D013329:Structure-Activity Relationship; D017855:Transferases (Other Substituted Phosphate Groups)
chemical_list: D010743:Phospholipids; D007294:Inositol; D010770:Phosphotransferases; D017855:Transferases (Other Substituted Phosphate Groups); D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase