Synthetic inositol 1,3,4,5-tetrakisphosphate analogues

Inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P₄] analogues were synthesized and their effects on [³H]Ins(1,3,4,5)P₄ 5-phosphatase, [³H]Ins(1,3,4,5)P₄ 3-phosphatase and [³H]inositol 1,4,5-trisphosphate [³H]Ins(1,4,5)P₃] 5-phosphatase activities were examined. The Ins(1,3,4,5)P₄ analogue with the aminobenzoyl group at the 2-position of Ins(1,3,4,5)P₄ inhibited the hydrolysis of 5-phosphate of [³H]Ins(1,3,4,5)P₄ catalysed by erythrocyte ghosts, with a lower K(i) value than seen with Ins(1,3,4,5)P₄, whereas the analogue with the aminocyclohexanecarbonyl group at the same position had a higher K(i) value. The Ins(1,4,5)P₃ analogues that we had previously synthesized were also capable of inhibiting this process, with the same tendency as Ins(1,3,4,5)P₄ analogues. Such differences in the potency among Ins(1,3,4,5)P₄ and Ins(1,4,5)P₃ analogues were applicable to other phosphatase activities, namely [³H]Ins(1,3,4,5)P₄ 3-phosphatase and [³H]Ins(1,4,5)P₃ 5-phosphatase. These results suggest that the active sites of these enzymes may catalyse the dephosphorylation in a similar fashion.