Regioselective approach to phosphatidylinositol 3,5-bisphosphates: Syntheses of the native phospholipid and biotinylated short-chain derivative

摘要

Figure presented A selective bis-silylation of 1D-O-TBDPS-myo-inositol leads to a 1,3,5-trisubstituted inositol, which can be advanced to the headgroup of phosphatidylinositol-3,5-bisphosphate [PI(3,5)P_2]. A mild, regioselective method for construction of the diacylglycerol moiety containing differing fatty acid chains, including the naturally occurring lipids, was developed. Their union in the synthesis of the cell-signaling molecule PI(3,5)P_2 containing the sn-1-stearoyl and sn-2-arachidonoyl groups is described. The methodology was also used to generate dioctanoyl-PI(3,5)P _2 and a previously unreported biotin-PI(3,5)P_2 conjugate, which was coupled to neutravidin beads and used to pull down PI(3,5)P _2-binding proteins from the cytosolic extract of adrenal neurosecretory cells. We report the specific pull-down of the PI(3,5)P _2-binding protein svp1p, a known PI(3,5)P_2 effector involved in membrane trafficking.