title: 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.
abstract: The synthesis of a novel and potent ligand at the D-myo-inositol 1,4, 5-trisphosphate receptor (InsP3R) is described. D-chiro-Inositol 1,3, 4,6-tetrakisphosphate (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-benzyl-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 the InsP3R 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), scyllo-inositol 1,2,4,5-tetrakisphosphate (4), D-myo-inositol 2,4,5-trisphosphate (5), and D-chiro-inositol 1, 3,4-trisphosphate (6). The protonation processes of 7 have also been investigated by 31P NMR titration experiments.
authors.affiliation: Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: R J
authors.initials: RJ
authors.lastname: Davis
authors.forename: S R
authors.initials: SR
authors.lastname: Nahorski
authors.forename: S
authors.initials: S
authors.lastname: Ballereau
authors.forename: B
authors.initials: B
authors.lastname: Spiess
authors.forename: B V
authors.initials: BV
authors.lastname: Potter
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008968:Molecular Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012996:Solutions; D013237:Stereoisomerism
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D012996:Solutions; C081653:inositol-1,3,4,6-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium