Synthesis, Separation, and Identification of Different Inositol Phosphates

  • Carsten Schultz
  • Anne Burmester
  • Christoph Stadler
Part of the Subcellular Biochemistry book series (SCBI, volume 26)


This review discusses recent progress in the synthesis of inositol phosphates and their analogues. Most of the research published prior to 1992 has been extensively reviewed (Potter and Nahorski, 1992; Potter, 1990; Billington, 1989), probably most completely in the book by Billington (1993). Therefore, mainly findings published since then and some of the most important earlier results are covered by this chapter. A brief discussion of the biochemistry of intracellular inositol phosphates in respect to cell signaling is presented, followed by some of the most crucial stereochemical aspects of inositol phosphates. The synthesis of naturally occurring myo-inositol phosphates and their synthetic derivatives is covered. In particular, the efforts to find agonists and antagonists of the most prominent inositol phosphate, myo-inositol-l,4,5-trisphosphate [Ins(1,4,5)P3], are summarized, including some of their biochemical properties. Finally, some of the most widely used techniques for separation and identification of inositol phosphates are presented.


Phytic Acid Inositol Phosphate Potent Agonist Cyclic Phosphate Inositol Polyphosphates 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations Used in this Chapter


myo-inositol-1,4,5-trisphosphate 3-kinase


myo-inositol polyphosphate 5-phosphatase




bis-(1,4)-diphosphoinositol tetrakisphosphate






intracellular free calcium concentration

cyclic AMP

cyclic adenosine monophosphate

cyclic GMP

cyclic guanosine monophosphate

cyclic InsP

cyclic myo-inositol monophosphate

cyclic InsP3

cyclic myo-inositol trisphosphate


di-myo-inositol-1,1′ -phosphate


gas chromatography




high performance liquid chromatography


concentration of unlabeled competitor that displaces half of specific binding


myo-inositol monophosphatase



InsP, InsP2

inositol mono-, bis-, tris-, tetrakis-, pentakis-, and hexa

InsP3, InsP4

kisphosphates, respectively, with assignment of phos

InsP5, and InsP6

phate locants where appropriate [e.g., Ins(l,4,5)P3]




myo-inositol hexakisphosphate


mass spectroscopy


nuclear magnetic resonance




1-diphosphoinositol pentakisphosphate


rat basophilic leukemia cells


rat embryo fibroblasts


human colon epithelial cell line


thin-layer chromatography






Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aguilo, A., Martin-Lomas, M., and Penades, S., 1992, The regioselective synthesis of enan-tiomerically pure myo-inositol derivatives: Efficient synthesis of myo-inositol 1,4,5-trisphosphate, Tetrahedron Lett. 33:401–404.Google Scholar
  2. Andersch, P., and Schneider, M. P., 1993, Enzyme assisted synthesis of enantiomerically pure myo-inositol derivatives—chiral building blocks for inositol polyphosphates, Tetrahedron: Asymmetry 4:2135–2138.Google Scholar
  3. Anejo, R., and Parra, A., 1994, Facile optical resolution of DL-1,4,5,6-tetra-O-benzyl myo-inositol: Key synthons for the phosphoinositides, Tetrahedron Lett. 35:525–526.Google Scholar
  4. Angyal, S. J., and Tate, M. E., 1961, Cyclitols. Part X. myo-inositol phosphates, J. Chem. Soc. 1961:4122–4128.Google Scholar
  5. Attwood, P. V., Ducep, J. B., and Chanal, M. C., 1988, Purification and properties of myo-inositol 1-phosphatase from bovine brain, Biochem. J. 253:387–394.PubMedGoogle Scholar
  6. Baker, R., Kulagowski, J. J., Billington, D. C., Leeson, P. D., Lennon, I. C., and Liverton, N. J., 1989, Synthesis of 2-and 6-deoxyinositol 1-phosphate and the role of the adjacent hydroxy groups in the mechanism of inositol monophosphatase, J. Chem. Soc. Chem. Commun. 1989:1383–1385.Google Scholar
  7. Baker, R., Leeson, P. D., Liverton, N. J., and Kulagowski, J. J., 1990, Identification of (IS)-phosphoryloxy-(2R,4S)-dihydroxycyclohexane as a potent inhibitor of inositol monophos-phatase, J. Chem. Soc. Chem. Commun. 1990:462–464.Google Scholar
  8. Baker, R., Carrick, C., Leeson, P. D., Lennon, I. C., and Liverton, N. J., 1991, Design and synthesis of 6α-substituted 2β,4α-dihydroxy-1β-phosphoryloxycyclohexanes, potent inhibitors of inositol monophosphatase, J. Chem. Soc. Chem. Commun. 1991:298–300.2Google Scholar
  9. Balla, T., Guillemette, G., Baukal, A. J., and Catt, K. J., 1987, Metabolism of inositol 1,3,4-trisphosphate to a new tetrakisphosphate isomer in angiotensin-stimulated adrenal glomerulosa cells, J. Biol. Chem. 262:9952–9955.PubMedGoogle Scholar
  10. Balla, T., Sim, S. S., Iida, T., Choi, K. Y., Catt, K. J., and Rhee, S. G., 1991, Agonist-induced calcium signalling is impaired in fibroblasts overproducing inositol 1,3,4,5-tetrakisphosphate, J. Biol. Chem. 266:24719–24726.PubMedGoogle Scholar
  11. Ballou, C. E., and Pizer, L. I., 1960, The absolute configuration of the myo-inositol 1-phosphates and a confirmation of the bornesitol configurations, J. Am. Chem. Soc. 82:3333–3335.Google Scholar
  12. Batty, I. R., Nahorski, S. R., and Irvine, R. F., 1985, Rapid formation of inositol 1,3,4,5-tetrakisphosphate following muscarinic receptor stimulation of rat cerebral cortical slices, Bio-chem. J. 232:211–215.Google Scholar
  13. Baudin, G., Glänzer, B. I., Swaminathan, K. S., and Vasella, A., 1988, A synthesis of 1D-and 1L-myo-inositol 1,3,4,5-tetrakisphosphate, Helv. Chim. Acta 71:1367–1378.Google Scholar
  14. Berridge, M. J., 1981, Phosphatidylinositol hydrolysis: A multifunctional transducing mechanism, Mol. Cell. Endocrinol. 24:115–140.PubMedGoogle Scholar
  15. Berridge, M. J., 1983, Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol, Biochem. J. 212:849–858.PubMedGoogle Scholar
  16. Berridge, M. J., 1993, Inositol trisphosphate and calcium signalling, Nature 361:315–325.PubMedGoogle Scholar
  17. Berridge, M. J., and Irvine, R. F., 1989, Inositol phosphates and cell signalling, Nature 341:197–205.PubMedGoogle Scholar
  18. Billington, D. C., 1989, Recent developments in the synthesis of myo-inositol phosphates, Chem. Soc. Rev. 18:83–122.Google Scholar
  19. Billington, D. C., 1993, The Inositol Phosphates: Chemical Synthesis and Biological Significance, Verlag Chemie, Weinheim.Google Scholar
  20. Bird, I. M., Sadler, I. H., Williams, B. C., and Walker, S. W., 1989, The preparation of myo-inositol 1,4-bisphosphate and D-myo-inositol 1,4,5-trisphosphate in milligram quantition from a readily available starting material, Mol. Cell. Endocrinol. 66:215–229.PubMedGoogle Scholar
  21. Brando, C., Hoffman, T., and Bonvini, E., 1990, High performance liquid chromatographic separation of inositol phosphate isomers employing a reversed phase column and a micellar mobile phase, J. Chromatogr. (Biomed. Appl.) 529:65–80.Google Scholar
  22. Bundgaard, H., 1993, Preparation of bioreversibly protected inositol phosphates as drugs, CA 119:9102t.Google Scholar
  23. Carless, H.A.J., and Busia, K., 1990, Total synthesis of chiro-inositol 2,3,5-trisphosphate: A myo-inositol 1,4,5-trisphosphate analogue from benzene via photo-oxidation, Tetrahedron Lett. 31:1617–1620.Google Scholar
  24. Cerdan, S., Hansen, C. A., Johanson, R., Inubushi, T., and Williamson, J. R., 1986, Nuclear magnetic resonance spectroscopic analysis of myo-inositol phosphates including inositol 1,3,4,5-tetrakisphosphate, J. Biol. Chem. 261:14676–14680.PubMedGoogle Scholar
  25. Challiss, R.A.J., and Nahorski, S. R., 1993, Measurement of inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, and phosphatidylinositol 4,5-bisphosphate in brain, Methods Neuro-sci. 18:224–244.Google Scholar
  26. Challiss, R.A.J., and Willcocks, A. L., Mulloy, B., Potter, B.V.L., and Nahorski, S. R., 1991, Characterization of inositol 1,4,5-trisphosphate-and inositol 1,3,4,5-tetrakisphosphate-binding sites in rat cerebellum, Biochem. J. 274:861–867.(1)PubMedGoogle Scholar
  27. Changya, L., Gallacher, D. V., Irvine, R. F., Potter, B.V.L., and Petersen, O. H., 1989, Inositol 1,3,4,5-tetrakisphosphate is essential for sustained activation of the Ca2+-dependent K+ current in single internally perfused mouse lacrimal acinar cells, J. Membr. Biol. 109:85–93.PubMedGoogle Scholar
  28. Chester, T. L., Pinkston, J. D., Innis, D. P., and Bowling, D. J., 1989, Separation, detection and identification of inositol trisphosphate and phytic acid derivatives by supercritical fluid chromatography and SFC-mass spectrometry, J. Microcolumn Sep. 1:182–189.Google Scholar
  29. Christensen, S., 1990, Serial separation of inositol phosphates including pentakis-and hexakisphos-phates on small anion exchange columns, J. Chromatogr. (Biomed. Appl.) 553:201–206.Google Scholar
  30. Chung, S.-K., and Moon, S.-H., 1994, Synthesis and biological activities of (4,6-di-O-phos-phonato-β-D-mannopyranosyl)-methylphosphonate as an analogue of 1 L-myo-inositol 1,4,5-trisphosphate, Carbohydrate Res. 260:39–50. (2)Google Scholar
  31. Cooke, A. M., Gigg, R., and Potter, B.V.L., 1987a, Synthesis of DL-myo-inositol 1,4,5-trisphosphate, Biochem. Soc. Trans. 15:904–906.Google Scholar
  32. Cooke, A. M., Gigg, R., and Potter, B.V.L., 1987b1987, myo-inositol 1,4,5-trisphosphorothioate: A novel analogue of a biological second messenger, J. Chem. Soc. Chem. Commun. 1987:1525–1526.Google Scholar
  33. Cooke, A. M., Nahorski, S. R., and Potter, B.V.L., 1989, myo-inositol 1,4,5-trisphosphorothioate is a potent competitive inhibitor of human erythrocyte 5-phosphates, FEBS Lett. 242:373–377. (3)PubMedGoogle Scholar
  34. Cullen, P. J., Irvine, R. F., and Dawson, A. P., 1990, Synergistic control of Ca2+ mobilization in permeabilized mouse L1210 lymphoma cells by inositol 2,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate, Biochem. J. 271:549–553.PubMedGoogle Scholar
  35. DeLisle, S., Radenberg, T., Wintermantel, M. R., Tietz, C., Parys, J. B., Pittet, D., Welsh, M. J., and Mayr, G. W., 1994, Second messenger specificity of the inositol trisphosphate receptor: Reappraisal based on novel inositol phosphates, Am. J. Physiol. 266:C429–C436.PubMedGoogle Scholar
  36. Downes, C. P., and MacPhee, C. H., 1990, myo-inositol metabolites as cellular signals, Eur. J. Biochem. 193:1–18.PubMedGoogle Scholar
  37. Dreef, C. E., Douwes, M., Elie, C.J.J., van der Marel, G. A., and van Boom, J. H., 1991a, Application of the bifuntional phosphonylating agent bis[6-(trifluoromethyl)benzotriazol-1-yl] methylphosphonate towards the preparation of isosteric D-myo-inositol phospholipid and phosphate analogues, Synthesis 1991:443–447.Google Scholar
  38. Dreef, C. E., Schiebler, W., van der Marel, G. A., and van Boom, J. H., 1991b, Synthesis of 5-phosphonate analogues of myo-inositol 1,4,5-trisphosphate: Possible intracellular calcium antagonists, Tetrahedron Lett. 32:6021–6024. (4)Google Scholar
  39. Drummond, A. H., 1987, Lithium and inositol lipid-linked signalling mechanisms, Trends Pharmacol. Sci. 8:129–133.Google Scholar
  40. Eckstein, F., and Gindl, H., 1968, Uridin-2′,3′-O,O-cyclothiophosphat, Chem. Ber. 101:1670–1673.PubMedGoogle Scholar
  41. Ely, J. A., Hunyady, L., Baukal, A. J., and Catt, K. J., 1990, Inositol 1,3,4,5-tetrakisphosphate stimulates calcium release from bovine adrenal microsomes by a mechanism independent of the inositol 1,4,5-trisphosphate receptor, Biochem. J. 268:333–338.PubMedGoogle Scholar
  42. Erneux, C., and Takazawa, K., 1991, Intracellular control of inositol phosphates by their metabolizing enzymes, Trends Pharmacol. Sci. 12:174–176.PubMedGoogle Scholar
  43. Estevez, V. A., and Prestwich, G. D., 1991a, Synthesis of enantiomerically pure, P-1 tethered inositol tetrakisphosphate affinity labels via a Ferner rearrangement, J. Am. Chem. Soc. 113:9885–9887.Google Scholar
  44. Estevez, V. A., and Prestwich, G. D., 1991b, Affinity probes for Ins(1,3,4,5)P4 receptors, Tetrahedron Lett. 32:1623–1626.Google Scholar
  45. Falck, J. R., and Abdali, A., 1993, Total synthesis of D-myo-inositol 3,4,5-trisphosphate and 1,3,4,5-tetrakisphosphate, Bioorg. Med. Chem. Lett. 3:717–720.Google Scholar
  46. Falck, J. R., and Yadagiri, P., 1989, Enantiospecific synthesis of D-myo-inositol 1,4,5-trisphosphate from (-)-quinic acid, J. Org. Chem. 54:5851–5852.Google Scholar
  47. Falck, J. R., Abdali, A., and Wittenberger, S. J., 1990, Total synthesis of the 5-methylenephospho-nate analogue of D-myo-inositol 1,4,5-trisphosphate, J. Chem. Soc. Chem. Commun. 1990: 953–955.Google Scholar
  48. Ferris, C. D., and Snyder, S. H., 1992, IP3 receptors: Ligand-activated calcium channels in multiple forms, in Advances in Second Messenger and Phosphoprotein Research, Vol. 26 (J. W. Putney, ed.), pp. 95–107, Raven Press, New York.Google Scholar
  49. Foster, P. S., Hogan, S. P., Hansbro, P. M., O’Brien, R., Potter, B.V.L., Ozaki, S., and Den-borough, M. A., 1994, The metabolism of D-myo-inositol trisphosphate and D-myo-inositol 1,3,4,5-tetrakisphosphate by porcine skeletal muscle, Eur. J. Biochem. 222:955–964.PubMedGoogle Scholar
  50. Freed, J. J., Farquhar, D., and Hampton, A., 1989, Evidence for acyloxymethyl esters of pyrimidine 5′-deoxyribonucleotides as extracellular sources of active 5′-deoxyribonucleotides in cultured cells, Biochem. Pharmacol. 38:3193–3198.PubMedGoogle Scholar
  51. Gawler, D. J., Potter, B.V.L., Gigg, R., and Nahorski, S. R., 1991, Interactions between inositol tris-and tetrakisphosphates, Biochem. J. 276:163–167. (5)PubMedGoogle Scholar
  52. Géro, S. G., 1966, The preparation of 1-O-tosyl-(-)-inositol from quebrachitol, Tetrahedron Lett. 6:591–595.PubMedGoogle Scholar
  53. Géro, S. G., Mercier, D., and Barrett, J. E., 1972, 1L-myo-Inositol 1-phosphate, Methods Car-bohydr. Chem. 6:403–408.Google Scholar
  54. Gigg, R., and Warren, C. D., 1969, Derivatvies of DL-2,3,4,5,6-penta-O-benzyl myo-inositol, J. Chem. Soc. 1969:2367–2371.Google Scholar
  55. Gill, D. L., Ghosh, T. K., and Mullaney, J. M., 1989, Calcium signalling mechanisms in endo-plasmatic reticulum activated by inositol 1,4,5-trisphosphate and GTP, Cell Calcium, 10:363–374.PubMedGoogle Scholar
  56. Goldman, H. D., Hsu, F.-F., and Sherman, W. R., 1990, Studies on the permethylation/ dephosphorylation of inositol polyphosphates: An approach to a more sensitive assay, Biomed. Environ. Mass Spectrom. 19:771–776.PubMedGoogle Scholar
  57. Goldschmidt, B., 1990, Preparative separation of myo-inositol bis-and trisphosphate isomers by anion exchange chromatography, Carbohydrate Res. 208:105–110.Google Scholar
  58. Grado, C., and Ballou, C. E., 1961, myo-Inositol phosphates obtained by alkaline hydrolysis of beef brain phosphoinositide, J. Biol. Chem. 236:54–60.PubMedGoogle Scholar
  59. Guédat, P., Spiess, B., and Schlewer, G., 1994, Synthesis of (+/-)-1,2-dideoxy-1,2-diamino myo-inositol, Tetrahedron Lett. 35:7375–7378.Google Scholar
  60. Guidot, J. P., and Le Gall, T., 1993a, Synthesis of a sulfur-containing analogue of myo-inositol, D,L-1-deoxy-l-mercapto-myo-inositol, via an intramolecular sulfur-delivery reaction, J. Org. Chem. 58:5271–5273.Google Scholar
  61. Guidot, J. P., and Le Gall, T., 1993b, Highly regioselective functionalization of a cis-1,2-diol in the myo-inositol series: Application to the synthesis of 2-deoxy-2-mercapto-myo-inositol, Tetrahedron Lett. 34:4647–4650.Google Scholar
  62. Hansbro, P. M., Foster, P. S., Liu, C., Potter, B.V.L., and Denborough, M. A., 1994, Kinetic analysis of novel inhibitors of inositol polyphosphate metabolism, Biochem. Biophys. Res. Commun. 200:8–15. (6)PubMedGoogle Scholar
  63. Hashii, M., Hirata, M., Ozaki, S., Nozawa, Y., and Higashida, H., 1994a Ca2+ influx evoked by inositol 3,4,5,6-tetrakisphosphate in ras-transformed NIH/3T3 fibroblasts, FEBS Lett. 340:276–280.PubMedGoogle Scholar
  64. Hawkins, P. T., Berrie, C. P., Morris, A. J., and Downes, C. P., 1987, Inositol 1:2-cyclic 4,5-trisphosphate is not a product of muscarinic receptor stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis in rat parotid glands, Biochem. J. 243:211–218.PubMedGoogle Scholar
  65. Henne, V., Mayr, G. W., Grabowski, B., Koppitz, B., and Söling, H.-D., 1988, Semisynthetic derivatives of inositol 1,4,5-trisphosphate substituted at the 1-phosphate group, Eur. J. Biochem. 174:95–101.PubMedGoogle Scholar
  66. Hirata, M., Watanabe, Y., Ishimatsu, T., Ikebe, T., Kimura, Y., Ymaguchi, K., Ozaki, S., and Koga, T., 1989, Synthetic inositol trisphosphate analogs and their effects on phosphatase, kinase, and the release of Ca2+, J. Biol. Chem. 264:20303–20308.PubMedGoogle Scholar
  67. Hirata, M., Watanabe, Y., Yoshida, M., Koga, T., and Ozaki, S., 1993, Roles for hydroxyl groups of D-myo-inositol 1,4,5-trisphosphate in the recognition by its receptor and metabolic enzymes, J. Biol. Chem. 268:19260–19266.PubMedGoogle Scholar
  68. Hokin-Neaverson, M., and Sadeghian, K., 1976, Separation of [3H]-inositol monophosphates and [3H]-inositol on silica gel glass-fiber sheets, J. Chromatogr. 120:502–505.PubMedGoogle Scholar
  69. Hsu, F.-F., Goldman, D., and Sherman, W. R., 1990, Thermospray liquid chromatographic/mass spectrometric studies with inositol phosphates, Biomed. Environ. Mass Spectrom. 19:597–600.PubMedGoogle Scholar
  70. Irvine, R. F. (ed.), 1990, Methods in Inositide Research, Raven Press, New York.Google Scholar
  71. Irvine, R. F., 1992, Is inositol tetrakisphosphate the second messenger that controls Ca2+ entry into cells, in Advances in Second Messenger and Phosphoprotein Research, Vol. 26 (J. W. Putney, ed.), pp. 161–185, Raven Press, New York.Google Scholar
  72. Irvine, R. F., and Moor, R. M., 1986, Micro-injection of inositol 1,3,4,5-tetrakisphosphate activates sea urchin eggs by a mechanism dependent on external Ca2+, Biochem. J. 240:917–920.PubMedGoogle Scholar
  73. Irvine, R. F., Änggard, E. E., Letcher, A. J., and Downes, C. P., 1985, Metabolism of inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate in rat parotid glands, Biochem. J. 229:505–511.PubMedGoogle Scholar
  74. Irvine, R. F., Letcher, A. J., Heslop, J. P., and Berridge, M. J., 1986, The inositol tris/tetrakisphos-phate pathway—demonstration of Ins(l,4,5)P3 3-kinase activity in animal tissues, Nature 320:631–634.PubMedGoogle Scholar
  75. Ishii, H., Connolly, T. M., Bross, T. E., and Majerus, P. W., 1986, Inositol cyclic trisphosphate [inositol 1,2-(cyclic)-4,5-trisphosphate] is formed upon thrombin stimulation of human platelets, Proc. Natl. Acad. Sci. USA 83:6397–6401.PubMedGoogle Scholar
  76. IUPAC, 1989, Numbering of atoms in myo-inositol, Biochem. J. 258:1–2.Google Scholar
  77. Jansen, A.B.A., and Russell, T. J., 1965, Some novel penicillin derivatives, J. Chem. Soc. 1965:2127–2132.Google Scholar
  78. Johansson, C., Koerdel, J., and Drakenberg, T., 1990, Analysis of myo-inositol phosphates by 2D proton NMR spectroscopy, Carbohydrate Res. 207:177–183.Google Scholar
  79. Johnson, S. C., Tagliaferri, F., and Baker, D. C., 1993, Synthesis of the 3-deoxy-3-C-(phosphonomethyl) analogue of 1 D-myo-inositol 3-(dihydrogenphosphate), Carbohydrate Res. 250:315–321.Google Scholar
  80. Kachintorn, U., Vajanaphanich, M., Barrett, K. E., and Traynor-Kaplan, A. E., 1993, Elevation of inositol tetrakisphosphate parallels inhibition of Ca2+-dependent Cl- secretion in T84 cells, Am. J. Physiol. 264:C671–C676.PubMedGoogle Scholar
  81. Kiely, D. E., Abruscato, G. J., and Baburao, V., 1974, A synthesis of myo-inositol 1-phosphate, Carbohydrate Res. 34:307–313.Google Scholar
  82. Kozikowski, A. P., Fauq, A. H., Powis, G., Kurian, P., and Crews, F. T., 1992, Expedient synthetic routes to [3H]-D-3-azido-deoxy-myo-inositol and D-3-azido-3-deoxy-myo-inositol 2,4,5-tris-phosphate, J. Chem. Soc. Chem. Commun. 1992:362–364. (10)Google Scholar
  83. Kozikowski, A. P., Ognyanov, V. I., Fauq, A. H., Nahorski, S. R., and Wilcox, R. A., 1993, Synthesis of 1D-3-deoxy-, 1D-2,3-dideoxy-, and 1D-2,3,6-trideoxy myo-inositol 1,4,5-trisphos-phate from quebrachitol, their binding affinities, and calcium release activity, J. Am. Chem. Soc. 115:4429–4434. (11)Google Scholar
  84. Kozikowski, A. P., Fauq, A. H., Wilcox, R. A., Challiss, R.A.J., and Nahorski, S. R., 1994a, The novel Ins(l,4,5)P3 analogue 3-amino-3-deoxy-Ins(l,4,5)P3: A pH-dependent Ins(1,4,5)P3 receptor partial agonist in SH-SY5Y neuroblastoma cells, J. Med. Chem. 37:868–872. (12)PubMedGoogle Scholar
  85. Kozikowski, A. P., Ognyanov, V. I., Fauq, A. H., Wilcox, R. A., and Nahorski, S. R., 1994b, 1D-myo-inositol 1,4,5-trisphosphate and 1D-myo-inositol 1,3,4,5-tetrakisphosphate analogues modified at C-3; synthesis of lD-3-C-(trifluoromethyl)-myo-inositol 1,4,5-trisphosphate and 1L-chiro inositol 1,2,3,5-tetrakisphosphate from L-quebrachitol, J. Chem. Soc. Chem. Commun. 1994:599–600.Google Scholar
  86. Kulagowski, J. J., 1989, The synthesis of ( + /-)-myo-inositol 1-phosphonate, Tetrahedron Lett. 30:3869–3872.Google Scholar
  87. Kulagowski, J. J., Baker, R., and Fletcher, S. R., 1991, Inhibitors of myo-inositol monophosphatase containing methylenebisphosphonic acid as a replacement for a phosphate group, J. Chem. Soc. Chem. Commun. 1991:1649–1650.Google Scholar
  88. Kurihara, N., Shibata, H., Saeki, H., and Nakajima, M., 1967, Synthesen von Inosit-monophosphaten, Liebigs Ann. Chem. 701:225–232.Google Scholar
  89. Lampe, D., and Potter, B.V.L., 1990, Synthesis of myo-inositol 1-phosphorothioate 4,5-bisphosphate: Preparation of a fluorescently labelled myo-inositol 1,4,5-trisphosphate analogue, J. Chem. Soc. Chem. Commun. 1990:1500–1502.Google Scholar
  90. Lampe, D., and Potter, B.V.L., 1993, Synthesis of 2-fluoro-2-deoxy myo-inositol 1,4,5-trisphosphate and scyllo-inositol 1,2,4-trisphosphate, novel analogues of the second messenger myo-inositol 1,4,5-trisphosphate, Tetrahedron Lett. 34:2365–2368.Google Scholar
  91. Leavitt, A. L., and Sherman, W. R., 1982a, Resolution of DL-myo-inositol 1-phosphate and other sugar enantiomers by gas chromatography, Methods Enzymol. 89:3–9.Google Scholar
  92. Leavitt, A. L., and Sherman, W. R., 1982b, Determination of inositol phosphates by gas chromatography, Methods Enzymol. 89:9–18.Google Scholar
  93. Leeson, P. D., James, K., Lennon, I. C., Liverton, N. J., Aspley, S., and Jackson, R. G., 1993, Adenosine-2′-monophosphate derivatives: Structural requirements as substrates for inositol monophosphatase, Bioorg. Med. Chem. Lett. 3:1925–1930.Google Scholar
  94. Leeuwen, van S. H., van der Marel, G. A., Hensel, R., and van Boom, J. H., 1994, Synthesis of LL-di-myo-inositol-1,1′-phosphate: A novel inositol phosphate from Pyrococcus woesi, Recl. Trav. Chim. Pays-Bas 113:335–336.Google Scholar
  95. Ley, S. V., Parra, M., Redgrave, A. J., and Sternfeld, F., 1990, Microbial oxidation in synthesis: Preparation of myo-inositol phosphates and related cyclitol derivatives from benzene, Tetrahedron 46:4995–5026.Google Scholar
  96. Lindon, J. C., Baker, D. J., Farrant, R. D., and Williams, J. M., 1986, 1H, 13C and 31P n.m.r. spectra and molecular conformation of myo-inositol 1,4,5-trisphosphate, Biochem. J. 233:275–277.PubMedGoogle Scholar
  97. Lindon, J. C., Baker, D. J., Williams, J. M., and Irvine, R. F., 1987, Conformation of the identities of inositol 1,3,4-trisphosphate and inositol 1,3,4,5-tetrakisphosphate by the use of one-dimensional and two-dimensional n.m.r. spectroscopy, Biochem. J. 244:591–595.PubMedGoogle Scholar
  98. Ling, L., and Ozaki, S., 1994, A chemoenzymatic synthesis of D-myo-inositol 1,4,5-trisphosphate, Carbohydrate Res. 256:49–58.Google Scholar
  99. Ling, L., Watanabe, Y., Akiyama, T., and Ozaki, S., 1992, A new efficient method for resolution of myo-inositol derivatives by enzyme catalyzed regio-and enantioselective esterifications in organic solvent, Tetrahedron Lett. 33:1911–1914.Google Scholar
  100. Liu, Y.-C., and Chen, C.-S., 1989, An efficient synthesis of optically active D-myo-inositol 1,4,5-trisphosphate, Tetrahedron Lett. 30:1617–1620.Google Scholar
  101. Maranto, A. R., 1994, Primary structure, ligand binding, and localization of the human type 3 inositol 1,4,5-trisphosphate receptor expressed in intestinal epithelium, J. Biol. Chem. 269: 1222–1230.PubMedGoogle Scholar
  102. Marecek, J. F., and Prestwich, G. D., 1989, Fluorinated analogs of Ins(1,4,5)P3, Tetrahedron Lett. 30:5401–5404.Google Scholar
  103. Mayr, G. W., 1988, A novel metal-dye detection system permits picomolar range h.p.l.c. analysis of inositol polyphosphates from non-radioactively labelled cell or tissue specimens, Biochem. J. 254:585–591.PubMedGoogle Scholar
  104. Mayr, G. W., and Dietrich, W., 1987, The only tetrakisphosphate detectable in avian erythrocytes is the isomer lacking phosphate at position 3: A NMR study, FEBS Lett. 213:278–282.PubMedGoogle Scholar
  105. Mayr, G. W., Radenberg, T., Thiel, U., Vogel, G., and Stephens, L. R., 1992, Phosphoinositol diphosphates: Non-enzymic formation in vitro and occurrence in vivo in the cellular slime mold Dictyostelium, Carbohydrate Res. 234:247–262.Google Scholar
  106. Meek, J. L., 1986, Inositol bis-, tris-, and tetrakis(phosphate)s: Analysis in tissues by HPLC, Proc. Natl. Acad. Sci. USA 83:4162–4166.PubMedGoogle Scholar
  107. Meek, J. L., and Nicoletti, F., 1986, Detection of inositol trisphosphate and other organic phosphates by high performance liquid chromatography using an enzyme-loaded post column reactor, J. Chromatogr. 351:303–311.Google Scholar
  108. Menitti, F. S., Oliver, K. G., Nogimori, K., Obie, J. F., Shears, S. B., and Putney, J. W., 1990, Origins of myo-inositol tetrakisphosphates in agonist-stimulated rat pancreatoma cells, J. Biol. Chem. 265:11167–11176.Google Scholar
  109. Menitti, F. S., Oliver, K. G., Putney, J. W., and Shears, S. B., 1993a, Inositol phosphates and cell signalling: New views of InsP5 and InsP6, Trends Biochem. Sci. 18:53–56.Google Scholar
  110. Menitti, F. S., Miller, R. N., Putney, J. W., and Shears, S. B., 1993b, Turnover of inositol polyphosphate pyrophosphates in pancreatoma cells, J. Biol. Chem. 268:3850–3856.Google Scholar
  111. Mercier, D., and Géro, S. D., 1968, The synthesis of (1S,2R,4R,5S,6R)-1,2,4,5,6-penta-O-benzoyl myo-inositol, Tetrahedron Lett. 31:3459–3462.Google Scholar
  112. Mercier, D., Barnett, J.E.G., and Géro, S. D., 1969, Synthesis of optically active derivatives of myo-inositol: Preparation of 1L-myo-inositol 1-phosphate, Tetrahedron 25:5681–5687.Google Scholar
  113. Metschies, T., 1990, Analoga des myo-Inositol-1-phosphats als Werkzeuge zur Aufklärung essentieller Wechselwirkungen der Inositmonophosphatase, Dissertation, Universität Bremen.Google Scholar
  114. Mikoshiba, K., 1993, Inositol 1,4,5-trisphosphate receptor, Trends Pharmacol. Sci. 14:86–89.PubMedGoogle Scholar
  115. Mills, S. J., Safrany, S. T., Wilcox, R. A., Nahorski, S. R., and Potter, B.V.L., 1993, Synthesis of myo-inositol 1,2,4,5-tetrakisphosphate, a Ca2+-mobilising tetrakisphosphate with a potency similar to myo-inositol 1,4,5-trisphosphate, Bioorg. Med. Chem. Lett. 3:1505–1510. (13)Google Scholar
  116. Nahorski, S. R., and Potter, B.V.L., 1989, Molecular recognition of inositol polyphosphates by intracellular receptors and metabolic enzymes, Trends Pharmacol. Sci. 10:139–144.PubMedGoogle Scholar
  117. Nahorski, S. R., Ragan, C. I., and Chaliss, R.A.J., 1991, Lithium and the phosphoinositide cycle: An example of uncompetitive inhibition and its pharmacological consequences, Trends Pharmacol. Sci. 12:297–303.PubMedGoogle Scholar
  118. Noble, N. J., Cooke, A. M., and Potter, B.V.L., 1992a, Synthesis of (+/-)-myo-inositol 1,4,5-trisphosphate and the novel analogue (+/-)-myo-inositol 1,4-bisphosphate 5-phosphorothioate, Carbohydrate Res. 234:177–187.Google Scholar
  119. Noble, N. J., Dubreuil, D., and Potter, B.V.L., 1992b, Total synthesis of myo-inositol 1-phosphate-4,5-pyrophosphate, a novel second messenger analogue, via myo-inositol l-phosphate-4,5-bisphosphorothioate, Bioorg. Med. Chem. Lett. 2:471–476. (14)Google Scholar
  120. Oliver, K. G., Putney, J. W., Obie, J. F., and Shears, S. B., 1992, The interconversion of inositol 1,3,4,5,6-pentakisphosphate and inositol tetrakisphosphates in AR4-2J cells, J. Biol. Chem. 267:21528–21534.PubMedGoogle Scholar
  121. Ozaki, S., Watanabe, Y., Ogasawara, T., Kondo, Y., Shiotani, N., Nishii, H., and Matsuki, T., 1986, Total synthesis of optically active myo-inositol 1,4,5-trisphosphate, Tetrahedron Lett. 27:3157–3160.Google Scholar
  122. Ozaki, S., Watanabe, Y., Ogasawara, T., Hirata, M., and Kanematsu, T., 1992, Synthesis and biological properties of 2-substituted myo-inositol 1,4,5-trisphosphate analogues directed toward affinity chromatography and photoaffinity labelling, Carbohydrate Res. 234:189–206.Google Scholar
  123. Ozaki, S., Ling, L., Ogasawara, T., Watanabe, Y., and Hirata, M., 1994, A convenient chemo-enzymatic synthesis of D-and L-myo-inositol 1,4,5,6-tetrakisphosphate, Carbohydrate Res. 259:307–310.Google Scholar
  124. Parthasarathy, R., and Eisenberg, F., 1986, The inositol phospholipids: A stereochemical view of biological activity, Biochem. J. 235:313–322.PubMedGoogle Scholar
  125. Paulsen, H., and Röben, W., 1983, Synthese von 1L-1-desoxy-1-C-hydroxymethyl-myo-inosit und 1L-1-desoxy-1-C-hydroxymethyl-chiro-inosit, Liebigs Ann. Chem. 1983:1073–1077.Google Scholar
  126. Pietrusiewicz, K. M., Salamonezyk, G. M., Bruzik, K. S., and Wieczork, W., 1992, The synthesis of homochiral inositol phosphates from myo-inositol, Tetrahedron 48:5523–5542.Google Scholar
  127. Polokoff, M. A., Bencen, G. H., Vacca, J. P., deSolms, S. J., Young, S. D., and Huff, J. R., 1988, Metabolism of synthetic inositol trisphosphate analogs, J. Biol. Chem. 263:11922–11927. (15)PubMedGoogle Scholar
  128. Potter, B.V.L., 1990, Recent advances in the chemistry and biochemistry of inositol phosphates of biological interest, Nat. Prod. Rep. 7:1–24.PubMedGoogle Scholar
  129. Potter, B.V.L., and Nahorski, S. R., 1992, Synthesis and biology of inositol polyphosphate analogues, Biochem. Soc. Trans. 20:434–442.PubMedGoogle Scholar
  130. Prestwich, G. D., Marecek, J. F., Mourey, R. J., Theibert, A. B., Ferris, C. D., Danoff, S. K., and Snyder, S. H., 1991, Tethered IP3: Synthesis and biochemical applications of the 1-O-(3-aminopropyl) ester of inositol 1,4,5-trisphosphate, J. Am. Chem. Soc. 113:1822–1825. (16)Google Scholar
  131. Prestwich, S. A., and Bolton, T. B., 1991, Measurement of picomole amounts of any inositol phosphate isomer separable by h.p.l.c. by means of a bioluminescence assay, Biochem. J. 274:663–672.PubMedGoogle Scholar
  132. Radenberg, T., Scholz, P., Bergmann, G., and Mayr, G. W., 1989, The quantitative spectrum of inositol phosphate metabolites in avian erythrocytes, analysed by proton n.m.r. and h.p.l.c. with direct isomer detection, Biochem. J. 264:323–333.PubMedGoogle Scholar
  133. Reese, C. B., and Ward, J. G., 1987, Synthesis of D-myo-inositol 1,4,5-trisphosphate, Tetrahedron Lett. 28:2309–2312.Google Scholar
  134. Russell, M.G.N., Baker, R., and Billington, D. C., 1992, The synthesis of 2-O-alkyl-myo-inositol 1-phosphates as competitive inhibitors of inositol monophosphatase, Carbohydrate Res. 234:263–286.Google Scholar
  135. Safrany, S. T., Wojcikiewicz, R.J.H., Strupish, J., McBain, J., Cooke, A. M., Potter, B.V.L., and Nahorski, S. R., 1991a, Synthetic phosphorothioate-containing analogues of inositol 1,4,5-trisphosphate mobilize intracellular Ca2+ stores and interact differentially with inositol 1,4,5-trisphosphate 5-phosphatase and 3-kinase, Mol. Pharmacol. 39:754–761.PubMedGoogle Scholar
  136. Safrany, S. T., Wojcikiewicz, R.J.H., Strupish, J., Nahorski, S. R., Dubreuil, D., Cleophax, J., Géro, S. D., and Potter, B.V.L., 1991b, Interaction of synthetic D-6-deoxy-myo-inositol 1,4,5-trisphosphate with the Ca2+-releasing D-myo-inositol 1,4,5-trisphosphate receptor, and the metabolic enzymes 5-phosphatase and 3-kinase, FEBS Lett. 278:252–256. (18)PubMedGoogle Scholar
  137. Safrany, S. T., Wilcox, R. A., Liu, C., Potter, B.V.L., and Nahorski, S. R., 1992a, 3-Position modification of myo-inositol 1,4,5-trisphosphate: Consequences for intracellular Ca2 + mobilisation and enzyme recognition, Eur. J. Pharmacol. 226:265–272. (19)PubMedGoogle Scholar
  138. Safrany, S. T., Sawyer, D. A., Nahorski, S. R., and Potter, B.V.L., 1992b, Synthetic D-and L-enantiomers of 2,2-difluoro-2-deoxy myo-inositol 1,4,5-trisphosphate interact differently with myo-inositol 1,4,5-trisphosphate binding proteins: Identification of a potent small molecule 3-kinase inhibitor, Chirality 4:415–422. (20)PubMedGoogle Scholar
  139. Safrany, S. T., Wilcox, R. A., Liu, C., Potter, B.V.L., and Nahorski, S. R., 1993, Identification of partial agonists with low intrinsic activity at the inositol-1,4,5-trisphosphate receptor, Mol. Pharmacol. 43:499–503. (21)PubMedGoogle Scholar
  140. Salamonczyk, G. M., and Pietrusiewicz, K. M., 1991, Expedient synthesis of D-myo-inositol 1,4,5-trisphosphate and D-myo-inositol 1,4-bisphosphate, Tetrahedron Lett. 32:6167–6170.Google Scholar
  141. Sastry, J. K., Nehete, P. N., Khan, S., Nowak, B. J., Plunkett, W., Arlinghaus, R. B., and Farquhar, D., 1992, Membrane-permeable dideoxyuridine 5′-monophosphate analogue inhibits human immunodeficiency virus infection, Mol. Pharmacol. 41:441–445.PubMedGoogle Scholar
  142. Schäfer, R., Nehls-Sahabandu, M., Grabowsky, B., Dehlinger-Kremer, M., Schulz, I., and Mayr, G. W., 1990, Synthesis and application of photoaffinity analogues of inositol 1,4,5-trisphosphate selectively substituted at the 1-phosphate group, Biochem. J. 272:817–825.PubMedGoogle Scholar
  143. Scholz, S., Sonnenbichler, J., Schäfer, W., and Hensel, R., 1992, Di-myo-inositol-1,1′-phosphate: A new inositol phosphate isolated from Pyrococcus woesi, FEBS Lett. 306:239–242.PubMedGoogle Scholar
  144. Schultz, C., and Tsien, R. Y., 1992, Membrane-permeant derivatives of inositolpolyphosphates applied to REF-52 fibroblasts, FASEB J. 6(5):A1924.Google Scholar
  145. Schultz, C., Metschies, T., Gerlach, B., Stadler, C., and Jastorff, B., 1990, Regioselective synthesis of inositol phosphate diesters via a cyclic phosphate triester approach, Synlett 1990:163–165.Google Scholar
  146. Schultz, C., Vajanaphanich, M., Barrett, K. E., Sammak, P. J., Harootunian, A. T., and Tsien, R. Y., 1993, Acetoxymethylesters of phosphates: Enhancement of the permeability and potency of cAMP, J. Biol. Chem. 268:6316–6322.PubMedGoogle Scholar
  147. Schultz, C., Vajanaphanich, M., Genieser, H.-G., Jastorff, B., Barrett, K. E., and Tsien, R. Y., 1994, Membrane-permeant derivatives of cAMP optimized for high potency, prolonged activity, or rapid reversibility, Mol. Pharmacol., 46:702–708.PubMedGoogle Scholar
  148. Seewald, M. J., Aksoy, I. A., Powis, G., Fauq, A. H., and Kozikowski, A. P., 1990, Synthesis of D-3-deoxy-myo-inositol 1,4,5-trisphosphate and its effect on Ca2+ release in NIH 3T3 cells, J. Chem. Soc. Chem. Commun. 1990:1502–1503.Google Scholar
  149. Sekar, M., Dixon, J. F., and Hokin, L. E., 1987, The formation of inositol 1:2-cyclic 4,5-trisphosphate and 1,2-cyclic 4-bisphosphate on stimulation of mouse pancreatic minilobules with carbamyl-choline, J. Biol. Chem. 262:340–344.PubMedGoogle Scholar
  150. Sharp, A. H., Snyder, S. H., and Nigam, S. K., 1992, myo-inositol 1,4,5-trisphosphate receptors. J. Biol. Chem. 267:7444–7449.PubMedGoogle Scholar
  151. Shayman, J. A., and Barcellon, F. S., 1990, Ion-pair chromatography of inositol polyphosphates with N-methylimipramine, J. Chromatogr. 528:143–152.PubMedGoogle Scholar
  152. Shayman, J. A., and BeMent, D. M., 1988, The separation of myo-inositol phosphates by ion-pair chromatography, Biochem. Biophys. Res. Commun. 151:114–122.PubMedGoogle Scholar
  153. Shayman, J. A., Morrison, A. R., and Lowry, O. H., 1987, Enzymatic fluorimetric assay for myo-inositol trisphosphate, Anal. Biochem. 162:562–568.PubMedGoogle Scholar
  154. Shears, S. B., 1992, Metabolism of inositol phosphates in Advances in Second Messenger and Phosphoprotein Research, Vol. 26 (J. W. Putney, ed.), pp. 63–92, Raven Press, New York.Google Scholar
  155. Sherman, W. R., Ackermann, K. E., Berger, R. A., Gish, B. G., and Zinbo, M., 1986, Analysis of inositol mono-and polyphosphates by gas chromatography/mass spectrometry and fast atom bombardment, Biomed. Environ. Mass Spectrom. 13:333–341.PubMedGoogle Scholar
  156. Shvets, V. I., Klyashchitskii, B. A., Stepanov, A. E., and Evstigneeva, R. P., 1973, Resolution of asymmetrically substituted myo-inositols into optical antipodes, Tetrahedron 29:331–340.Google Scholar
  157. Sinha, N. D., Biernat, J., McManus, J., and Köster, H., 1984, Polymer support oligonucleotide synthesis XVIII: Use of β-cyanoethyl-N,N-dialkylamino/N-morpholino phosphoroamidite of deoxynucleosides for the synthesis of DNA fragments simplifying deprotection and isolation of the final product, Nucleic Acids Res. 12:4539–4557.PubMedGoogle Scholar
  158. Smith, R. E., and MacQuarrie, R. A., 1988, Determination of inositol phosphates and other biologically important anions by ion chromatography, Anal. Biochem. 170:308–315.PubMedGoogle Scholar
  159. Srivastva, D. N., and Farquhar, D., 1984, Bioreversible phosphate protective groups: Synthesis and stability of model acyloxymethyl phosphates, Bioorg. Chem. 12:118–129.Google Scholar
  160. Stepanov, A. E., and Shvets, V. I., 1979, Synthetic studies of phosphoinositides, Chem. Phys. Lipids 25:247–263.Google Scholar
  161. Stephens, L., and Downes, C. P., 1990, Product-precursor relationships amongst inositol polyphosphates, Biochem. J. 265:435–452.PubMedGoogle Scholar
  162. Stephens, L., Hawkins, P. T., Barker, C. J., and Downes, C. P., 1988, Synthesis of myo-inositol 1,3,4,5,6-pentakisphosphate from inositol phosphates generated by receptor activation, Biochem. J. 253:721–733.PubMedGoogle Scholar
  163. Stephens, L., Radenberg, T., Thiel, U., Vogel, G., Khoo, K.-H., Dell, A., Jackson, T. R., Hawkins, P. T., and Mayr, G. W., 1993, The detection, purification, structural characterization, and metabolism of diphosphoinositol pentakisphosphate(s) and bisdiphosphoinositol tetrakisphos-phate(s), J. Biol. Chem. 268:4009–4015.PubMedGoogle Scholar
  164. Streb, H., Irvine, R. F., Berridge, M. J., and Schulz, I., 1983, Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol 1,4,5-trisphosphate, Nature 306:67–69.PubMedGoogle Scholar
  165. Sulpice, J.-C., Gascard, P., Journet, E., Rendu, F., Renard, D., Poggioli, J., and Giraud, F., 1989, The separation of [32P]-inositol phosphates by ion-pair chromatography: Optimization of the method and biological applications, Anal. Biochem. 179:90–97.PubMedGoogle Scholar
  166. Takahashi, M., Tanzawa, K., and Takahashi, S., 1994, Adenophostins, newly discovered metabolites of Penicillium brevicompactum, act as potent agonists of the inositol 1,4,5-trisphosphate receptor, J. Biol. Chem. 269:369–372. (22)PubMedGoogle Scholar
  167. Takahashi, S., Kinoshita, T., and Takahashi, M., 1994, Adenophostins A and B: Potent agonists of inositol 1,4,5-trisphosphate receptor produced by Pencillium brevicompactum Structure elucidation, J. Antibiot. 47:95–100.PubMedGoogle Scholar
  168. Tate, M. E., 1968, Separation of myo-inositol pentaphosphates by moving paper electrophoresis (MPE), Anal. Biochem. 23:141–149.PubMedGoogle Scholar
  169. Tegge, W., and Ballou, C. E., 1989, Chiral synthesis of D-and L-myo-inositol 1,4,5-trisphosphate, Proc. Natl. Acad. Sci. USA 86:94–98.PubMedGoogle Scholar
  170. Tegge, W., and Ballou, C. E., 1992, Syntheses of D-myo-inositol 1,4,5-trisphosphate affinity lig-ands, Carbohydrate Res. 230:63–77.Google Scholar
  171. Tegge, W., Denis, G. V., and Ballou, C. E., 1991, Synthesis and Ca2+-release activity of D-and L-chiro-inositol 1,3,4-trisphosphate, Carbohydrate Res. 217:107–116. (23)Google Scholar
  172. Tsien, R. W., and Tsien, R. Y., 1990, Calcium channels, stores, and oscillations, Annu. Rev. Cell Biol. 6:715–760.PubMedGoogle Scholar
  173. Tsien, R. Y., 1981, A non-disruptive technique for loading calcium buffers and indicators into the cells, Nature 290:527–528.PubMedGoogle Scholar
  174. Turk, J., Wolf, B. A., and McDaniel, M. L., 1986, Quantitation of myo-inositol as its hexa-kis(trifluoroacetyl) derivative with negative ion chemical ionization mass spectrometry, Biomed. Environ. Mass Spectrom. 13:237–244.PubMedGoogle Scholar
  175. Vajanaphanich, M., Schultz, C., Rudolf, M. T., Wasserman, M, Enyedi, P., Craxton, A., Shears, S. B., Tsien, R. Y., Barrett, K. E., and Traynor-Kaplan, A. E., 1994, Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4, Nature 371:711–714.PubMedGoogle Scholar
  176. Walker, J. W., Feeney, J., and Trentham, D. R., 1989, Photolabile precursors of inositol phosphates: Preparation and properties of 1-(2-nitrophenyl)ethyl esters of myo-inositol 1,4,5-trisphosphate, Biochemistry 28:3272–3280.PubMedGoogle Scholar
  177. Watanabe, Y., Mitani, M., Morita, T., and Ozaki, S., 1989, Highly efficient protection by the tetraisopropyldisiloxane-1,3-diyl group in the synthesis of myo-inositol phosphates as inositol 1,3,4,6-tetrakisphosphate, J. Chem. Soc. Chem. Commun. 1989:482–483.Google Scholar
  178. Watanabe, Y., Shinohara, T., Fujimoto, T., and Ozaki, S., 1990, A short step and practical synthesis of myo-inositol 1,3,4,5-tetrakisphosphate, Chem. Pharm. Bull. 38:562–563.Google Scholar
  179. Watanabe, Y., Fujimoto, T., Shinohara, T., and Ozaki, S., 1991, A short step synthesis of optically active myo-inositol 1,3,4,5-tetrakisphosphate and myo-inositol 1,4,5-trisphosphate from 1,3,5-tri-O-benzoyl myo-inositol, J. Chem. Soc. Chem. Commun. 1991:428–429.Google Scholar
  180. Watanabe, Y., Ogasawara, T., Ozaki, S., and Hirata, M., 1994, Synthesis of myo-inositol 1,4,6-trisphosphate, an analogue of myo-inositol 1,4,5-trisphosphate, Carbohydrate Res. 258:87–92.Google Scholar
  181. Westerduin, P., Willems, H.A.M., and van Boeckel, C.A.A., 1990, Total synthesis of new 1,5-bissubstituted myo-inositol derivatives: Synthesis of D-myo-inositol 1,5-bisphosphate and of rac. 1,5-bissulphated and 1,5-bissulphamoylated isosteric analogues, Tetrahedron Lett. 31:6915–6918.Google Scholar
  182. Westerduin, P., Willems, H.A.M., and van Boeckel, C.A.A., 1992, Synthesis of analogues of myo-inositol 1,4,5-trisphosphate that contain sulfonamide, sulfate, methylphosphonate, and carboxy-methyl groups, Carbohydrate Res. 234:131–140.Google Scholar
  183. Wilcox, R. A., Nahorski, S. R., Sawyer, D. A., Liu, C., and Potter, B.V.L., 1992, The role of the 2-and 3-hydroxyl groups of 1D-myo-inositol 1,4,5-trisphosphate in the mobilisation of calcium from permealized human 1321N1 astrocytoma cells, Carbohydrate Res. 234:237–246. (24)Google Scholar
  184. Wilcox, R. A., Challiss, R.A.J., Liu, C., Potter, B.V.L., and Nahorski, S. R., 1993, Inositol 1,3,4,5-tetrakisphosphate induces calcium mobilization via the inositol 1,4,5-trisphosphate receptor in SH-SY5Y neuroblastoma cells. Mol. Pharmacol. 44:810–817. (25)PubMedGoogle Scholar
  185. Wilcox, R. A., Safrany, S. T., Lampe, D., Mills, S. J., Nahorski, S. R., and Potter, B.V.L., 1994, Modification at C2 of myo-inositol 1,4,5-trisphosphate produces inositol trisphosphates and tetrakisphosphates with potent biological activities, Eur. J. Biochem. 223:115–124. (26)PubMedGoogle Scholar
  186. Willcocks, A. L., Potter, B.V.L., Cooke, A. M., and Nahorski, S. R., 1988, myo-Inositol 1,4,5-trisphosphorothioate binds to specific [3H]-inositol 1,4,5-trisphosphate sites in rat cerebellum and is resistant to 5-phosphatase, Eur. J. Pharmacol. 155:181–183. (27)PubMedGoogle Scholar
  187. Willcocks, A. L., Strupish, J., Irvine, R. F., and Nahorski, S. R., 1989, Inositol 1:2-cyclic 4,5-trisphosphate is only a weak agonist at inositol 1,4,5-trisphosphate receptors, Biochem. J. 257:197–200. (28)Google Scholar
  188. Wong, N. S., Barker, C. J., Shears, S. B., Kirk, C. J., and Michell, R. H., 1988, Inositol 1:2-cyclic 4,5-trisphosphate is not a major product of inositol phospholipid metabolism in vasopressin stimulated WRK1 cells, Biochem. J. 252:1–5.PubMedGoogle Scholar
  189. Wreggett, K. A., and Irvine, R. F., 1987, A rapid separation method for inositol phosphates and their isomers, Biochem. J. 245:655–660.PubMedGoogle Scholar
  190. Wreggett, K. A., Howe, L. R., Moore, J. P., and Irvine, R. F., 1987, Extraction and recovery of inositol phosphates from tissues, Biochem. J. 245:933–934.PubMedGoogle Scholar
  191. Yu, K.-L., and Fraser-Reid, B., 1988, A novel reagent for the synthesis of myo-inositol phosphates: N,N-Diisopropyl dibenzyl phosphoramidite, Tetrahedron Lett. 29:979–982.Google Scholar
  192. Zhou, M., Hu, Y., Schultz, C., Kandel, E. R., and Hawkins, R. D., 1994, Role of guanylyl cyclase and cGMP-dependent protein kinse in long-term potentiation, Nature 368:635–639.Google Scholar
  193. Zilberman, Y., Howe, L. R., Moore, J. P., Hesketh, T. R., and Metcalfe, J. C., 1987, Calcium regulates inositol 1,3,4,5-tetrakisphosphate production in lysed thymocytes and in intact cells stimulized with concanvalin A, EMBO J. 6:957–962.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • Carsten Schultz
    • 1
  • Anne Burmester
    • 1
  • Christoph Stadler
    • 1
  1. 1.Institute for Organic Chemistry, Laboratory of Bioorganic ChemistryUniversity of BremenBremenGermany

Personalised recommendations