有机磷农药/有机磷神经性毒剂的蛋白加合物及其加合机制研究进展

Research progress of organophosphorus pesticides/organophosphorus nerve agents′protein adducts and formation mechanism

有机磷农药(organophosphorus pesticides,OPP)和有机磷神经性毒剂(organophosphorus nerve agents,OPNAs)属于有机磷领域中重要的化合物,主要通过不可逆的抑制乙酰胆碱酯酶(acetylcholinesterase,AChE)发挥毒性作用。该文以蛋白加合物为研究对象,通过研究OPP/OPNAs与不同的靶蛋白:内源性清道夫(丁酰胆碱酯酶、白蛋白、转铁蛋白)和低剂量毒性的相关蛋白(细胞骨架蛋白、神经病靶标酯酶、泛素)形成的共价加合物,深度剖析蛋白加合物的形成机制、活性位点的结构特征,以期为之后有机磷(organophosphorus,OP)毒物的确认暴露、溯源归因、精准治疗、合理预防等提供新思路。

Organophosphorus pesticides(OPP)and organophosphorus nerve agents(OPNAs)are both toxic organophosphorus compounds,which mainly exert toxic effects through irreversible inhibition of acetylcholinesterase(AChE).This paper takes protein adducts as the research objective,studying the covalent adducts formed by OPP/OPNAs and different target proteins:endogenous scavengers(butyrylcholinesterase,albumin,transferrin)and low-dose toxicity related proteins(Cytoskeleton protein,neuropathic target esterase,ubiquitin).The formation mechanism of protein adducts and the structural characteristics of active sites are reviewed for providing new ideas to confirm the exposure,trace,and accurate treatment and reasonable prevention of OP poisons in the future.