Inframolecular studies of the protonation of 1D-1,2,4/3,5-cyclopentanepentaol 1,3,4-trisphosphate, a ring-contracted analogue of 1D-myo-inositol 1,4,5-trisphosphate

The protonation process of the individual phosphate groups of 1D-1,2,4/3,5-cyclopentanepentol 1,3,4-trisphosphate has been investigated by 31P NMR titration experiments. The results are compared with those of 1D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. From the NMR titration curves it can be shown that P3 and P4 strongly interact, whereas P1 behaves independently. In addition, P3 and P4 are much less influenced by their vicinal hydroxyls than P1. Accordingly, the calculated microscopic protonation constants indicate a higher basicity for P3 and P4 compared with the basicity of P1. The vicinal bisphosphate of the cyclopentane-based compounds seems to adopt a similar conformation to that of Ins(1,4,5)P3, although an analogous interaction with a hydroxyl group is not observed. Two cyclopentanepentaol trisphosphates were examined for their potency to release intracellular Ca2+ from rat hepatocytes. Both were found to be low-affinity agonists in this regard. The relationship of this activity to the physicochemical data is discussed for one example. Copyright (C) 1999 Elsevier Science Ltd.