CYTOTOXICITY OF DICHLOROMETHANE DIPHOSPHONATE AND OF 1-HYDROXYETHANE-1,1-DIPHOSPHONATE IN THE AMEBAS OF THE SLIME-MOLD DICTYOSTELIUM-DISCOIDEUM - A P-31 NMR-STUDY

被引：51

作者：

PELORGEAS, S ^{[1
]}

MARTIN, JB ^{[1
]}

SATRE, M ^{[1
]}

机构：

[1] UJF,CEN G,DEPT BIOL MOLEC & STRUCT,RESONANCE MAGNET BIOL & MED LAB,CEA GRP,CNRS,INSERM,F-38041 GRENOBLE,FRANCE

来源：

BIOCHEMICAL PHARMACOLOGY | 1992年 / 44卷 / 11期

关键词：

D O I：

10.1016/0006-2952(92)90342-G

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Two pyrophosphate analogues, dichloromethane diphosphonate (Cl2MDP), and 1-hydroxyethane-1,1-diphosphonate (EHDP), at concentrations of 0.5-1 mM, efficiently inhibited the growth of amoebae of the slime mould Dictyostelium discoideum. Cell viability decreased markedly upon incubation with the diphosphonates. The mechanism of toxicity was investigated by in vivo P-31 NMR spectroscopy and the formation of analogues of ATP [adenosine 5'-(beta,gamma-dichloromethane triphosphate) and adenosine 5'-(beta,gamma-1-hydroxyethane triphosphate)] was demonstrated. These two compounds were identified from their P-31 NMR spectra in perchloric acid extracts prepared from amoebae poisoned with Cl2MDP or EHDP and may have been synthesized by reversible pyrophosphate exchange catalysed by cytosolic aminoacyl-tRNA synthetases.

引用

页码：2157 / 2163

页数：7

共 23 条

[1] 3 NEW BETA,GAMMA-METHYLENE ANALOGS OF ADENOSINE-TRIPHOSPHATE [J].