AND D-MYOINOSITOL-1,4,5-TRIPHOSPHATE AND THEIR ANALOGS THE LONG-TERM OBJECTIVE OF THIS PROPOSAL ARE: (1) TO DEVELOP A GENERAL METHOD FOR THE SYNTHESIS OF PHOSPHATIDYL- D-MYOINOSITOL-4,5-BISPHOSPHATE [PTDINS(4,5)P2] AS A KEY MATERIAL FOR THE PREPARATION

AND D-MYOINOSITOL-1,4,5-TRIPHOSPHATE AND THEIR ANALOGS THE LONG-TERM OBJECTIVE OF THIS PROPOSAL ARE: (1) TO DEVELOP A GENERAL METHOD FOR THE SYNTHESIS OF PHOSPHATIDYL- D-MYOINOSITOL-4,5-BISPHOSPHATE [PTDINS(4,5)P2] AS A KEY MATERIAL FOR THE PREPARATION OF D-MYO-INOSITOL-1,4,5- TRIPHOSPHATE [INS(1,4,5)P2] AND A VARIETY OF ANALOGS; (2) TODESIGN AND PREPARE THESE COMPOUNDS; AND (3) TO EVALUATE THEIR APPLICATIONS FOR INVESTIGATING THE MECHANISM OF HORMONE-INDUCED INTRACELLULAR CA2+ RELEASE AND SIGNAL TRANSMISSION. A GENERAL SCHEME OF SYNTHESIS STARTING FROM NATURAL PHOSPHATIDYLINOSITOL [PTDINS] IS PROPOSED. DURING PHASE I, USING A RELAY STRATEGY, PTDINS(4,5)P2 FROM BEEF- BRAIN PHOSPHOINOSITIDES WILL BE CONVERTED INTO 1-AMINODEOXY-GLYCEROPHOSPHO-D-MYO-INOSITOL-4',5'-BISPHOSPHATE, AND GLYCEROPHOSPHOINOSITOL-4,5-BISPHOSPHATE. THE TWO COMPOUNDS WILL THEN BE COMPARED IN MODEL STUDIES AS CANDIDATE ANALOGS FOR LINKING TO PHOTOLABILE GROUPS, AND TO INERT SUPPORTS FORUSE AS POTENTIAL AIDS FOR THE CHARACTERIZATION AND PURIFICATION OF THE INS(1,4,5)P3-BINDING PROTEIN. ALSO DURING PHASE I, KEY STEPS IN THE PROPOSED GENERAL SCHEME WILL BE INVESTIGATED TO EXPERIMENTALLY DETERMINE THE FEASIBILITY OF THE OVERALL STRATEGY FOR SYNTHESIS STARTING FROM PTDINS.