Metabolically stabilized derivatives of phosphatidylinositol 4-phosphate: Synthesis and applications

Ju He, Joanna Gajewiak, Jordan L. Scott, Denghuang Gong, Muzaffar Ali, Michael D. Best, Glenn D. Prestwich, Robert V. Stahelin, Tatiana G. Kutateladze

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Phosphatidylinositol 4-phosphate (PtdIns(4)P) lipid is an essential component of eukaryotic membranes and a marker of the Golgi complex. Here, we developed metabolically stabilized (ms) analogs of PtdIns(4)P and the inositol 1,4-bisphosphate (IP 2) head group derivative and demonstrated that these compounds can substitute the natural lipid fully retaining its physiological activities. The methylenephosphonate (MP) and phosphorothioate (PT) analogs of PtdIns(4)P and the aminohexyl (AH)-IP 2 probe are recognized by the PtdIns(4)P-specific PH domain of four phosphate adaptor protein 1 (FAPP1). Binding of FAPP1 to the PtdIns(4)P derivatives stimulates insertion of the PH domain into the lipid layers and induces tubulation of membranes. Both ms analogs and IP 2 probes could be invaluable for identifying protein effectors and characterizing PtdIns(4)P-dependent signaling cascades within the trans-Golgi network (TGN).

Original languageEnglish (US)
Pages (from-to)1312-1319
Number of pages8
JournalChemistry and Biology
Volume18
Issue number10
DOIs
StatePublished - Oct 28 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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    He, J., Gajewiak, J., Scott, J. L., Gong, D., Ali, M., Best, M. D., Prestwich, G. D., Stahelin, R. V., & Kutateladze, T. G. (2011). Metabolically stabilized derivatives of phosphatidylinositol 4-phosphate: Synthesis and applications. Chemistry and Biology, 18(10), 1312-1319. https://doi.org/10.1016/j.chembiol.2011.07.022