二氯甲烷二膦酸盐和1-羟基乙烷-1,1-二膦酸盐对黏菌盘基网柄菌变形虫的细胞毒性。一项³¹P核磁共振研究。

Cytotoxicity of dichloromethane diphosphonate and of 1-hydroxyethane-1,1-diphosphonate in the amoebae of the slime mould Dictyostelium discoideum. A 31P NMR study.

作者信息

Pelorgeas S, Martin J B, Satre M

机构信息

Département de Biologie Moléculaire et Structurale, Groupement CEA-CNRS-INSERM-UJF, Grenoble, France.

出版信息

Biochem Pharmacol. 1992 Dec 1;44(11):2157-63. doi: 10.1016/0006-2952(92)90342-g.

DOI:10.1016/0006-2952(92)90342-g

PMID:1472080

Abstract

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 31P 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 31P 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.

摘要

两种焦磷酸盐类似物，二氯甲烷二膦酸盐（Cl2MDP）和1-羟基乙烷-1,1-二膦酸盐（EHDP），浓度为0.5-1 mM时，能有效抑制黏菌盘基网柄菌变形虫的生长。与二膦酸盐一起孵育后，细胞活力显著下降。通过体内31P核磁共振波谱研究了毒性机制，并证实了ATP类似物[腺苷5'-（β，γ-二氯甲烷三磷酸）和腺苷5'-（β，γ-1-羟基乙烷三磷酸）]的形成。这两种化合物是从用Cl2MDP或EHDP中毒的变形虫制备的高氯酸提取物的31P核磁共振波谱中鉴定出来的，可能是由胞质氨酰-tRNA合成酶催化的可逆焦磷酸盐交换合成的。