Metabolically Stabilized Derivatives of Phosphatidylinositol 4-Phosphate: Synthesis and Applications

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• 作者：Ju He¹ ;   ; ⁷ ; Joanna Gajewiak² ;   ; ⁷ ; Jordan  ; L. Scott³ ;   ; ⁴ ;   ; ⁷ ; Denghuang Gong⁵ ; Muzaffar Ali¹ ; Michael  ; D. Best⁵ ; Glenn  ; D. Prestwich² ; Robert  ; V. Stahelin³ ;   ; ⁴ ;   ; ⁶ ; Tatiana  ; G. Kutateladze¹ ;   ; ^{tatiana.kutateladze@ucdenver.edu}
• 刊名：Chemistry & Biology
• 出版年：2011
• 出版时间：28 October 2011
• 年：2011
• 卷：18
• 期：10
• 页码：1312-1319
• 全文大小：1343 K

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Summary

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 (IP₂) 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)-IP₂ 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 IP₂ probes could be invaluable for identifying protein effectors and characterizing PtdIns(4)P-dependent signaling cascades within the trans-Golgi network (TGN).