SYNTHESIS OF 1D-3-DEOXY-MYO-INOSITOL, 1D-2,3-DIDEOXY-MYO-INOSITOL, AND 1D-2,3,6-TRIDEOXY-MYO-INOSITOL 1,4,5-TRISPHOSPHATE FROM QUEBRACHITOL, THEIR BINDING AFFINITIES, AND CALCIUM-RELEASE ACTIVITY

Syntheses of three optically pure, deoxygenated myo-inositol 1,4,5-trisphosphate analogues from quebrachitol are reported together with their binding affinities and Ca-45(2+) release activity. The ligand-binding affinities of the analogues were determined using membrane preparations from bovine adrenal cortex. The Ca-45(2+) release activities were compared to that of Ins(1,4,5)P3, using the calcium mobilizing receptor of saponin permeabilized SH-SY5Y human neuroblastoma cells. 1D-3-deoxy-Ins(1,4,5)P3 (26) and 1D-2,3-dideoxy-Ins(1,4,5)P3 (22) exhibited very potent ligand and agonist properties, while 1D-2,3,6-trideoxy-Ins(1,4,5)P3 (19) was much less potent. These data provide solid evidence of the critical role which HO-6 of Ins(1,4,5)P3 plays in its binding affinity and its Ca2+ mobilizing activity.