Synthesis, calcium mobilizing, and physicochemical properties of D-chiro-inositol 1,3,4,6-tetrakisphosphate, a novel and potent ligand at the D-myo-inositol 1,4,5-trisphosphate receptor

The synthesis of a novel and potent ligand at the D-myo-inositol 1,4,5-tris phosphate receptor (InsP(3)R) is described. D-chiro-Inositol 1,3,4,6-tetrak isphosphate (7) and L-chiro-inositol 1,3,4,6-tetrakisphosphate (ent-7) have been synthesized from D-2,5-di-O-benzyl-chiro-inositol and L-2,5-di-O-benz yl-chiro-inositol, respectively. The potency of binding and Ca2+ release of 7 and ent-7 were examined in L15 and Lvec cells. 7 was a full agonist at t he InsP(3)R in both cells, and ent-7 was inactive. The results are compared to those from D-myo-inositol 1,4,5-trisphosphate (1), DL-scyllo-inositol 1 ,2,4-trisphosphate (2), DL-myo-inositol 1,2,4,5-tetrakisphosphate (3), scyl lo-inositol 1,2,4,5-tetrakisphosphate (4), D-myo-inositol 2,4,5-trisphospha te (5), and D-chiro-inositol 1,3,4-trisphosphate (6). The protonation proce sses of 7 have also been investigated by P-31 NMR titration experiments.