Liu C, Davis R J, Nahorski S R, Ballereau S, Spiess B, Potter B V
Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
J Med Chem. 1999 Jun 3;42(11):1991-8. doi: 10.1021/jm980733i.
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.
本文描述了一种新型强效D-肌醇1,4,5-三磷酸受体（InsP3R）配体的合成。D-手性肌醇1,3,4,6-四磷酸酯（7）和L-手性肌醇1,3,4,6-四磷酸酯（对映体-7）分别由D-2,5-二-O-苄基-手性肌醇和L-2,5-二-O-苄基-手性肌醇合成。在L15和Lvec细胞中检测了7和对映体-7的结合能力及Ca2+释放能力。7在两种细胞的InsP3R上均为完全激动剂，而对映体-7无活性。将结果与D-肌醇1,4,5-三磷酸酯（1）、DL-青蟹肌醇1,2,4-三磷酸酯（2）、DL-肌醇1,2,4,5-四磷酸酯（3）、青蟹肌醇1,2,4,5-四磷酸酯（4）、D-肌醇2,4,5-三磷酸酯（5）和D-手性肌醇1,3,4-三磷酸酯（6）的结果进行了比较。还通过31P NMR滴定实验研究了7的质子化过程。
