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  • 标题:Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo
  • 本地全文:下载
  • 作者:Denis G. Ilyushin ; Ivan V. Smirnov ; Alexey A. Belogurov
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2013
  • 卷号:110
  • 期号:4
  • 页码:1243-1248
  • DOI:10.1073/pnas.1211118110
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The creation of effective bioscavengers as a pretreatment for exposure to nerve agents is a challenging medical objective. We report a recombinant method using chemical polysialylation to generate bioscavengers stable in the bloodstream. Development of a CHO-based expression system using genes encoding human butyrylcholinesterase and a proline-rich peptide under elongation factor promoter control resulted in self-assembling, active enzyme multimers. Polysialylation gives bioscavengers with enhanced pharmacokinetics which protect mice against 4.2 LD50 of S-(2-(diethylamino)ethyl) O-isobutyl methanephosphonothioate without perturbation of long-term behavior.
  • 关键词:organophosphate ; N-acetylneuraminic acid ; Russian VX ; pesticide ; mass spectrometry
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