Long ciuculating liposomes encapsulating organophosphorus acid anhydrolase in diisopropylfluorophosphate antagonism
Long ciuculating liposomes encapsulating organophosphorus acid anhydrolase in diisopropylfluorophosphate antagonism
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DOI：
10.1093/toxsci/57.1.16
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发表时间：
2000-09-01
影响因子：
3.8
通讯作者：
Way, JL
中科院分区：
文献类型：
--
作者：
Petrikovics, I;Cheng, TC;Way, JL
这些研究主要集中在对抗有机磷（OP）中毒的一种新的概念方法，即用空间稳定脂质体包裹的重组酶来增强二异丙基氟磷酸（DFP）的降解。包裹在脂质体内的OP水解酶，有机磷酸酐酶（OPAA），可以单独使用，也可以与普拉多肟（2-PAM）和/或阿托品联合使用。来自Alteromonas菌株JD6的重组OPAA酶对多种OP化合物（如DFP、soman和沙林）具有高底物特异性。采用氟离子选择电极测定氟离子浓度变化，测定含OPAA (SL)*脂质体对DFP的水解速率。该酶载体系统为op代谢酶（OPAA）提供了可生物降解的保护环境，从而增强了对DFP致死效应的解毒剂保护。单独游离OPAA有一定的解毒作用；然而，2-PAM和/或阿托品与(SL)*联合使用时，保护作用大大增强。
These studies are focused on antagonizing organophosphorous (OP) intoxications by a new conceptual approach using recombinant enzymes encapsulated wit-hin sterically stabilized liposomes to enhance diisopropylfluorophosphate (DFP) degradation. The OP hydrolyzing enzyme, organophosphorous acid anhydrolase (OPAA), encapsulated within the liposomes, was employed either alone or in combination with pralidoxime (2-PAM) and/or atropine. The recombinant OPAA enzyme, from the Alteromonas strain JD6, has high substrate specificity toward a wide range of OP compounds, e.g., DFP, soman, and sarin. The rate of DFP hydrolysis by liposomes containing OPAA (SL)* was measured by determining the changes in fluoride-ion concentration using a fluoride ion-selective electrode. This enzyme carrier system serves as a biodegradable protective environment for the OP-metabolizing enzyme (OPAA), resulting in an enhanced antidotal protection against the lethal effects of DFP. Free OPAA alone showed some antidotal protection; however, the protection with 2-PAM and/or atropine was greatly enhanced when combined with (SL)*.