关键词: biological scavenger detoxification directed evolution organophosphorus poisoning

来  源:   DOI:10.1093/toxres/tfae089   PDF(Pubmed)

Abstract:
UNASSIGNED: Organophosphorus compounds, widely used in agriculture and industry, pose a serious threat to human health due to their acute neurotoxicity. Although traditional interventions for organophosphate poisoning are effective, they often come with significant side effects.
UNASSIGNED: This paper aims to evaluate the potential of enzymes within biological organisms as organophosphorus bioclearing agents. It analyses the technical challenges in current enzyme research, such as substrate specificity, stereoselectivity, and immunogenicity, while exploring recent advancements in the field.
UNASSIGNED: A comprehensive review of literature related to detoxifying enzymes or proteins was conducted. Existing studies on organophosphorus bioclearing agents were summarised, elucidating the biological detoxification mechanisms, with a particular focus on advancements in protein engineering and novel delivery methods.
UNASSIGNED: Current bioclearing agents can be categorised into stoichiometric and catalytic bioclearing agents, both of which have shown some success in preventing organophosphate poisoning. Technological advancements have significantly improved various properties of bioclearing agents, yet challenges remain, particularly in substrate specificity, stereoselectivity, and immunogenicity. Future research will focus on expanding the substrate spectrum, enhancing catalytic efficiency, prolonging in vivo half-life, and developing convenient administration methods.
UNASSIGNED: With the progression of clinical trials, bioclearing agents are expected to become widely used as a new generation of therapeutic organophosphate detoxifiers.
摘要:
有机磷化合物,广泛用于农业和工业,因其具有急性神经毒性而对人类健康造成严重威胁。尽管传统的有机磷中毒干预措施是有效的,它们经常伴随着显著的副作用。
本文旨在评估生物有机体中酶作为有机磷生物净化剂的潜力。它分析了当前酶研究中的技术挑战,如底物特异性,立体选择性,和免疫原性,同时探索该领域的最新进展。
对与解毒酶或蛋白质相关的文献进行了全面综述。总结了有关有机磷生物净化剂的现有研究,阐明生物解毒机制,特别关注蛋白质工程和新型递送方法的进步。
目前的生物净化剂可分为化学计量和催化生物净化剂,两者都在预防有机磷中毒方面取得了一些成功。技术进步显著改善了生物净化剂的各种性能,然而挑战依然存在,特别是在底物特异性方面,立体选择性,和免疫原性。未来的研究将集中在扩展底物光谱上,提高催化效率,延长体内半衰期,并开发方便的管理方法。
随着临床试验的进展,生物净化剂有望被广泛用作新一代治疗性有机磷酸酯解毒剂。
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