Synthesis, Calcium Mobilizing, and Physicochemical Properties of <SCP>d</SCP>-chiro-Inositol 1,3,4,6-Tetrakisphosphate, a Novel and Potent Ligand at the <SCP>d</SCP>-myo-Inositol 1,4,5-Trisphosphate Receptor

The synthesis of a novel and potent ligand at the <SCP>d</SCP>-myo-inositol 1,4,5-trisphosphate receptor (InsP<INF>3</INF>R) is described. <SCP>d</SCP>-chiro-Inositol 1,3,4,6-tetrakisphosphate (<BO>7</BO>) and <SCP>l</SCP>-chiro-inositol 1,3,4,6-tetrakisphosphate (ent-<BO>7</BO>) have been synthesized from <SCP>d</SCP>-2,5-di-O-benzyl-chiro-inositol and <SCP>l</SCP>-2,5-di-O-benzyl-chiro-inositol, respectively. The potency of binding and Ca²⁺ release of <BO>7</BO> and ent-<BO>7</BO> were examined in L15 and Lvec cells. <BO>7</BO> was a full agonist at the InsP<INF>3</INF>R in both cells, and ent-<BO>7</BO> was inactive. The results are compared to those from <SCP>d</SCP>-myo-inositol 1,4,5-trisphosphate (<BO>1</BO>), <SCP>dl</SCP>-scyllo-inositol 1,2,4-trisphosphate (<BO>2</BO>), <SCP>dl</SCP>-myo-inositol 1,2,4,5-tetrakisphosphate (<BO>3</BO>), scyllo-inositol 1,2,4,5-tetrakisphosphate (<BO>4</BO>), <SCP>d</SCP>-myo-inositol 2,4,5-trisphosphate (<BO>5</BO>), and <SCP>d</SCP>-chiro-inositol 1,3,4-trisphosphate (<BO>6</BO>). The protonation processes of <BO>7</BO> have also been investigated by ³¹P NMR titration experiments.