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: J D Moyer, O Reizes, S Ahir, C Jiang, N Malinowski, D C Baker
• Journal: Molecular pharmacology (Mol Pharmacol) Vol. 33 Issue 6 Pg. 683-9 (Jun 1988) ISSN: 0026-895X [Print] United States
• PMID: 2837638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Phospholipids
• Inositol
• Phosphotransferases
• Transferases (Other Substituted Phosphate Groups)
• CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase

Topics

• CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase
• Inositol (analogs & derivatives, metabolism)
• Models, Molecular
• Phospholipids (metabolism)
• Phosphotransferases
• Structure-Activity Relationship
• Transferases (Other Substituted Phosphate Groups)