Li Hexi, Lu Cong, Liu Zhenmin, Xiang Fengshun, Liu Bo, Wang Hongjuan, Chang Jie, Pan Li, Chen Youwei, Chen Jingfei
Institute of NBC Defence, PLA, ARMY, 1 North Street, Yangfang Town, Changping District, Beijing 102205, China.
Unit No. 31666 of PLA, 1 New City Courtyard, Jinyang Town, Liangzhou District, Wuwei, Gansu 733000, China.
Toxicol Res (Camb). 2024 Jun 10;13(3):tfae089. doi: 10.1093/toxres/tfae089. eCollection 2024 Jun.
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.
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.
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.
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.
With the progression of clinical trials, bioclearing agents are expected to become widely used as a new generation of therapeutic organophosphate detoxifiers.
有机磷化合物广泛应用于农业和工业,因其急性神经毒性对人类健康构成严重威胁。尽管传统的有机磷中毒干预措施有效,但往往伴有显著的副作用。
本文旨在评估生物体内的酶作为有机磷生物清除剂的潜力。分析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。总结了现有的有机磷生物清除剂研究,阐明了生物解毒机制,特别关注蛋白质工程和新型递送方法的进展。
当前的生物清除剂可分为化学计量型和催化型生物清除剂,两者在预防有机磷中毒方面均取得了一定成功。技术进步显著改善了生物清除剂的各种性能,但挑战依然存在,尤其是在底物特异性、立体选择性和免疫原性方面。未来的研究将集中在扩大底物谱、提高催化效率、延长体内半衰期以及开发便捷的给药方法。
随着临床试验的推进,生物清除剂有望作为新一代治疗性有机磷解毒剂得到广泛应用。