Increased organophosphate scavenging in a butyrylcholinesterase mutant

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• 作者：Brian C. Geyer ; Ryan R. Woods ; Tsafrir S. Mor
• 关键词：Bioscavenger ; Transgenic plants ; Nerve agents ; Molecular pharming ; Cocaine hydrloase ; Pesticides
• 刊名：Chemico-Biological Interactions
• 出版年：2008
• 出版时间：25 September 2008
• 年：2008
• 卷：175
• 期：1-3
• 页码：376-379
• 全文大小：267 K

文摘

Nicotiana benthamiana plant lines expressing a reengineered human butyrylcholinesterase (BChE) with enhanced cocaine hydrolase activity were created. Subsequent purification and biochemical analysis revealed that compared to wild-type butyrylcholinesterase, the cocaine hydrolase displayed increased affinity to the organophosphate (OP) pesticides paraoxon (6.84 × 10⁻¹⁰ M vs. 1.11 × 10⁻⁸ M) and malaoxon (9.81 × 10⁻⁸ M vs. 5.99 × 10⁻⁷ M). Furthermore, the cocaine hydrolase retained identical anticholinesterase binding profiles for all other compounds tested. Thus we have demonstrated a potential large-scale production platform for a multivalent antidote for cocaine and anticholinesterase poisoning.