Synthesis and Cellular Labeling of Multifunctional Phosphatidylinositol Bis? and Trisphosphate Derivatives

We synthesized the first multifunctionalized phosphoinositide polyphosphate derivatives featuring a photo-removable protecting group (“cage”), photo-crosslinkable diazirine group, and terminal alkyne useful for click chemistry. demonstrate that lipid readily enter cells. After photo-crosslinking, cell fixation fluorescent tagging via chemistry, we determined intracellular location of before after uncaging lipids. find there is rapid trafficking PI(3,4)P2 PI(3,4,5)P3 to plasma membrane, opening intriguing possibility active transport these lipids involved. employed photo-crosslinking chemistry functions analyze proteome PI(3,4,5)P3-binding proteins. From latter, validated by RNAi putative binding proteins ATP11A MPP6 are involved in membrane.