Centre de Recherches du Service de Santé des Armées, Toxicology department, La Tronche, France;
Acta Naturae. 2009 Apr;1(1):68-79.
Bioscavengers are biopharmaceuticals that specifically react with toxicants. Thus, enzymes reacting with poisonous esters can be used as bioscavengers for neutralization of toxic molecules before they reach physiological targets. Parenteral administration of bioscavengers is, therefore, intended for prophylaxis or pre-treatments, emergency and post-exposure treatments of intoxications. These enzymes can also be used for application on skin, mucosa and wounds as active components of topical skin protectants and decontamination solutions. Human butyrylcholinesterase is the first stoichiometric bioscavenger for safe and efficient prophylaxis of organophosphate poisoning. However, huge amounts of a costly enzyme are needed for protection. Thus, the bioscavenger approach will be greatly improved by the use of catalytic bioscavengers. Catalytic bioscavengers are enzymes capable of degrading toxic esters with a turnover. Suitable catalytic bioscavengers are engineered mutants of human enzymes. Efficient mutants of human butyrylcholinesterase have been made that hydrolyze cocaine at a high rate. Mutants of human cholinesterases capable of hydrolyzing OPs have been made, but so far their activity is too low to be of medical interest. Human paraoxonase a promiscuous plasma enzyme is certainly the most promising phosphotriesterase. However, its biotechnology is still in its infancy. Other enzymes and proteins from blood and organs, and secondary biological targets of OPs and carbamates are potential bioscavengers, in particular serum albumin that reacts with OPs and self-reactivates. Lastly, non-human enzymes, phosphotriesterases and oxidases from various bacterial and eukaryotic sources could be used for external use against OP poisoning and for internal use after modifications for immunological compatibility.
生物清除剂是专门与毒物发生反应的生物制药。因此，能与有毒酯类反应的酶可以作为生物清除剂，在有毒分子到达生理靶点之前将其中和。因此，生物清除剂的肠胃外给药旨在进行预防或预处理、中毒的紧急和暴露后治疗。这些酶也可以作为局部皮肤保护剂和去污溶液的有效成分应用于皮肤、粘膜和伤口。人丁酰胆碱酯酶是用于安全有效地预防有机磷中毒的第一个化学计量生物清除剂。然而，需要大量昂贵的酶来进行保护。因此，使用催化生物清除剂将极大地改善生物清除剂方法。催化生物清除剂是能够以周转率降解有毒酯类的酶。合适的催化生物清除剂是人类酶的工程突变体。已经制造出了高效突变体人丁酰胆碱酯酶，可高速水解可卡因。已经制造出了能够水解 OPs 的人胆碱酯酶的突变体，但到目前为止，它们的活性太低，没有医学意义。人对氧磷酶是一种混杂的血浆酶，肯定是最有前途的磷酸三酯酶。然而，其生物技术仍处于起步阶段。血液和器官中的其他酶和蛋白质，以及 OPs 和氨基甲酸酯的次级生物靶标，特别是与 OPs 反应并自我激活的血清白蛋白，都是潜在的生物清除剂。最后，非人类酶，来自各种细菌和真核生物的磷酸三酯酶和氧化酶，可用于外部抵抗 OP 中毒，以及经过免疫相容性修饰后用于内部使用。
